JP6879740B2 - How to Treat Lymphatic Plasma Cell Lymphoma - Google Patents

Description

Related Applications This application relates to US Provisional Patent Application USSN 62 / 036,934 filed on August 13, 2014, and USSN 61 / 915,684 filed on December 13, 2013, 35 U.S.A. S. C. Claim priority under § 119 (e), the entire contents of which are incorporated herein by reference.

Government Support The present invention was made under the grants 5R01CA130876-05, 5P50CA090578-10, 5R01CA136851-04, 2R01CA136851-05 and 1R01CA172592-01A1 granted to the National Cancer Institute with the support of the United States Government. The US Government has certain rights in the present invention.

Background of the Invention Waldenström macroglobulinemia (WM) is a distinct clinicopathological disease unit that results from the accumulation of clonally associated lymphatic plasma cells that secrete clonal IgM proteins, primarily in the bone marrow. Is. This condition is considered to correspond to lymphoplasmacytic lymphoma (LPL) as defined by the World Health Organization classification system. WM is a rare disease in the United States with less than 1,500 cases occurring annually. There is a 2- to 3-fold risk of developing WM in people with an individual history of autoimmune disease due to autoantibodies, and a particularly increased risk associated with hepatitis, human immunodeficiency virus, and rickettsia (Arch. Intern. Med., 2008, 168 (17), 1903-9). There is no accepted treatment for WM and there can be significant changes in clinical outcomes. The response rate is high (> 80%), but the complete response rate is low (0 to 15%) (Clin. Adv. Hematol. Oncol., 2009, 7 (10), 677-81, 687-90). Therefore, there is a need for effective treatment of WM.

の化合物またはその医薬的に許容可能な塩であって、式中、Ｑ、Ｕ、Ｒ^Ａ、Ｒ^Ｂ、Ｒ^Ｘ、ｋおよびｌは、本明細書において定義される、の発見に基づく。
これらの化合物の活性は、いくつかのキナーゼ（例えばBTK、HCK、TAK1、HPK1）に対するin vitroスクリーニングにより確立した。 The present invention, at least in part, for the treatment of Waldenström macroglobulinemia, formula (A):

A compound or a pharmaceutically acceptable salt thereof, wherein, Q, U, R A, R B, R X, k and l are defined herein, based on the discovery of.
The activity of these compounds was established by in vitro screening for several kinases (eg BTK, HCK, TAK1, HPK1).

およびその医薬的に許容可能な塩である。 In some embodiments, the compound of formula (A) is of formula:

And its pharmaceutically acceptable salt.

およびその医薬的に許容可能な塩に関する。 Another aspect of the present invention is the compound of formula (I-11):

And its pharmaceutically acceptable salts.

のいずれか一つの化合物およびその医薬的に許容可能な塩であって、式中、環Ａ’、環Ｃ’、Ｃｙ、Ｘ’、Ｙ’、Ｚ’、Ｑ’、Ｕ’、Ｒ^Ａ’、Ｒ^Ｂ’、Ｒ^Ｄ’、Ｒ^Ｘ’、ｋ’、ｌ’およびｍ’は、本明細書において定義されるとおりである、も提供する。 The present invention also includes formula (II) or (V) :.

Any one compound of the above and a pharmaceutically acceptable salt thereof, wherein the ring A', ring C', Cy, X', Y', Z', Q', U', ^RA ' , R ^B ', R ^D ', ^RX ', k', l'and m'are also provided, as defined herein.

The present invention is also based on the discovery that Waldenstram macrogamma globulinemia can be treated, at least in part, by administration of a compound of the invention to a subject in need thereof. The activity of these compounds is an in vitro screen for several kinases (eg, BTK, HCK, TAK1, HPK1) involved in the regulation of abnormal cell proliferation, as well as a disease state model of Waldenstrem macrogamma globulinemia. Some cell lines (eg BCWM.1, MWCL-1) (Ditzel et al. Exp Hematol. 2007 Sep; 35 (9): 1366-75; Hodge et al. Blood. 2011 May 12; 117 (19) )) Established by cell-based screening.

Methods of treatment utilizing the compounds of the invention also include Hodgkin's lymphoma, as well as many non-Hodgkin's lymphomas such as diffuse large B-cell lymphoma, follicular lymphoma, mucosal-related lymphoid lymphoma (MALT), small lymphocytic. Lymphoma (overlapping with chronic lymphocytic leukemia), mantle cell lymphoma (MCL), Berkit lymphoma, medial large cell type B cell lymphoma, nodular marginal zone B cell lymphoma (NMZL), splenic marginal zone lymphoma (SMZL) ), Intravascular large B-cell lymphoma, primary exudative lymphoma, and lymphoma-like granulomatosis.

The present invention, at least in part, is a compound of the invention (eg, a compound of formula (A), (I-11), (II) or (V) (eg, formula (A-1)-(A-18). ) Compound)) based on a pharmaceutical composition comprising a pharmaceutically acceptable excipient. In some embodiments, the pharmaceutical composition is associated with an abnormal activity of the kinase in vitro or in a subject in need thereof to regulate the activity of the kinase and / or in a subject in need thereof. It can be useful for treating and / or preventing a condition (eg, a proliferative disorder). In some embodiments, the pharmaceutical composition may be useful for the treatment of Waldenstrem macrogamma globulinemia in a subject in need thereof.

The present invention also comprises compounds of the invention (eg, compounds of formulas (A), (I-11), (II) or (V) (eg, compounds of formulas (A-1)-(A-18)). ), Or a kit in a container containing the pharmaceutical composition thereof. The kit may include a single dose or multiple doses of the compounds described herein or their pharmaceutical compositions. The kit can be useful for regulating the activity of kinases in subjects who need it. The kit can also be useful for treating and / or preventing conditions associated with the abnormal activity of kinases in subjects in need of it. In some embodiments, the kit further comprises instructions for using the kit (eg, for administering a compound described herein or a pharmaceutical composition thereof).

Details of certain aspects of the invention are described herein. Other features, objectives and advantages of the present invention will be apparent from the detailed description, drawings, examples and claims.

Definitions Chemical Definitions Definitions of specific functional groups and chemical terms are described in more detail below. Chemical elements are identified according to the Handbook of Chemistry and Physics, 75th Edition, Periodic Table of the Elements, CAS version, and specific functional groups are generally defined as described herein. In addition, general principles of organic chemistry, as well as specific functional moieties and reactivity, are described in Organic Chemistry, Thomas Sorrell, University Science Books, Sausalito, 1999; Smith and March, March's Advanced Organic Chemistry, 5th Edition, John Wiley & Sons, Inc., New York, 2001; Larock, Comprehensive Organic Transformations, VCH Publishers, Inc., New York, 1989; and Carruthers, Some Modern Methods of Organic Synthesis, 3rd Edition, Cambridge University Press, Cambridge, 1987. Listed in the year.

The compounds described herein may contain one or more asymmetric centers and can therefore be present in a variety of stereoisomeric forms, such as enantiomers and / or diastereomers. For example, the compounds described herein may be in the form of individual enantiomers, diastereomers or geometric isomers, or may include racemic mixtures and mixtures rich in one or more stereoisomers. It may be in the form of a mixture of three isomers. The isomers can be isolated from the mixture by methods known to those skilled in the art, including chiral high performance liquid chromatography (HPLC) and the formation and crystallization of chiral salts; or the preferred isomers can be isolated by asymmetric synthesis. Can be prepared. For example, Jacques et al., Enantiomers, Racemates and Resolutions (Wiley Interscience, New York, 1981); Wilen et al., Tetrahedron 33: 2725 (1977); Eliel, EL Stereochemistry of Carbon Compounds (McGraw-Hill, NY, 1962). Year); and see Wilen, SH Tables of Resolving Agents and Optical Resolutions p. 268 (EL Eliel, Univ. Of Notre Dame Press, Notre Dame, IN 1972). The present invention further includes compounds as individual isomers that are substantially free of other isomers, or as a mixture of various isomers.

Unless otherwise stated, the structures represented herein are also meant to contain compounds that differ only in the presence of atoms enriched with one or more isotopes. For example, compounds having this structure are within the scope of the present disclosure, except for hydrogen replacement with deuterium or tritium, 19F replacement with 18F, or carbon replacement with carbon enriched with 13C or 14C. Such compounds are useful, for example, as analytical tools or probes in biological assays.

When a range of values is listed, it is intended to include each value and subrange within the range. For example, "C _1-6 alkyl" is C ₁ , C ₂ , C ₃ , C ₄ , C ₅ , C ₆ , C _1-6 , C _1-5 , C _1-4 , C _1-3 , C _{1 -2} , C _2-6 , C _2-5 , C _2-4 , C _2-3 , C _3-6 , C _3-5 , C _3-4 , C _4-6 , C _4-5 and C ₅ It is intended to include _{-6 alkyl.}

The term "aliphatic" as used herein refers to alkyl, alkenyl, alkynyl and carbocyclic groups. Similarly, the term "heteroaliphatic" as used herein refers to heteroalkyl, heteroalkenyl, heteroalkynyl and heterocyclic groups.

The term "alkyl" refers to radicals of linear or branched saturated hydrocarbon groups with 1-10 carbon atoms ("C _1-10 alkyl"). In some embodiments, the alkyl group has 1-9 carbon atoms (“C _1-9 alkyl”). In some embodiments, the alkyl group has 1 to 8 carbon atoms (“C _1-8 alkyl”). In some embodiments, the alkyl group has 1-7 carbon atoms (“C _1-7 alkyl”). In some embodiments, the alkyl group has 1 to 6 carbon atoms (“C _1-6 alkyl”). In some embodiments, the alkyl group has 1-5 carbon atoms (“C _1-5 alkyl”). In some embodiments, the alkyl group has 1 to 4 carbon atoms (“C _1-4 alkyl”). In some embodiments, the alkyl group has 1-3 carbon atoms (“C _1-3 alkyl”). In some embodiments, the alkyl group has 1-2 carbon atoms (“C _1-2 alkyl”). In some embodiments, the alkyl group has one carbon atom ( "C ₁ alkyl"). In some embodiments, the alkyl group has 2 to 6 carbon atoms (“C _2-6 alkyl”). Examples of C _1-6 alkyl groups are methyl (C ₁ ), ethyl (C ₂ ), propyl (C ₃ ) (eg n-propyl, isopropyl), butyl (C ₄ ) (eg n-butyl, tert-butyl). , Se-butyl, iso-butyl), pentyl (C ₅ ) (eg n-pentyl, 3-pentanyl, amyl, neopentyl, 3-methyl-2-butanyl, tertiary amyl), and hexyl (C ₆ ) (eg n-hexyl). Further examples of alkyl groups include n-heptyl (C ₇ ), n-octyl (C ₈ ) and the like. Unless otherwise specified, each of the alkyl groups is independently unsubstituted (“unsubstituted alkyl”) or by one or more substituents (eg, halogens such as F). Substituted (“substituted alkyl”). In some embodiments, the alkyl group is an unsubstituted C _1-10 alkyl (such as an unsubstituted C _1-6 alkyl, such as −CH ₃ (Me), an unsubstituted ethyl (Et), an unsubstituted propyl (Pr, eg, an unsubstituted n). -Propyl (n-Pr), unsubstituted isopropyl (i-Pr)), unsubstituted butyl (Bu, eg, unsubstituted n-butyl (n-Bu), unsubstituted tert-butyl (tert-Bu or t-Bu)) , Unsubstituted sec-butyl (sec-Bu), unsubstituted isobutyl (i-Bu)). In some embodiments, the alkyl group is substituted C _1-10 alkyl (substituted C _1-6 alkyl, etc., eg-CF. ₃ , Bn).

As used herein, a "haloalkyl" is a substituted alkyl group as defined herein, wherein one or more of the hydrogen atoms are independently halogenated. For example, it is replaced by fluoro, bromo, chloro or iodine. "Perhaloalkyl" is a subset of haloalkyl and refers to an alkyl group in which all hydrogen atoms are independently replaced by a halogen, such as fluoro, bromo, chloro or iodine. In some embodiments, the haloalkyl moiety has 1 to 8 carbon atoms (“C _1-8 haloalkyl”). In some embodiments, the haloalkyl moiety has 1 to 6 carbon atoms (“C _1-6 haloalkyl”). In some embodiments, the haloalkyl moiety has 1 to 4 carbon atoms (“C _1-4 haloalkyl”). In some embodiments, the haloalkyl moiety has 1-3 carbon atoms (“C _1-3 haloalkyl”). In some embodiments, the haloalkyl moiety has 1-2 carbon atoms (“C _1-2 haloalkyl”). In some embodiments, all hydrogen atoms of the haloalkyl are replaced with fluoro to provide a perfluoroalkyl group. In some embodiments, all hydrogen atoms of the haloalkyl are replaced with chloro to provide a "perchloroalkyl" group. Examples of haloalkyl groups include -CF ₃ , -CF ₂ CF ₃ , -CF ₂ CF ₂ CF ₃ , -CCl ₃ , -CFCl ₂ , -CF ₂ Cl and the like.

As used herein, a "heteroalkyl" is an alkyl group as defined herein, in the parent chain (ie, inserted between adjacent carbon atoms in the parent chain). And / or at least one heteroatom selected from oxygen, nitrogen or sulfur (eg, one, two, three or four heteroatoms) located at one or more ends of the parent chain. ) Is further included. In some embodiments, a heteroalkyl group refers to a saturated group having 1 to 10 carbon atoms and one or more heteroatoms in the parent chain (“hetero C _1-10 alkyl”). In some embodiments, the heteroalkyl group is a saturated group having 1 to 9 carbon atoms and one or more heteroatoms in the parent chain (“hetero C _1-9 alkyl”). In some embodiments, the heteroalkyl group is a saturated group having 1 to 8 carbon atoms and one or more heteroatoms in the parent chain (“hetero C _1-8 alkyl”). In some embodiments, the heteroalkyl group is a saturated group having 1 to 7 carbon atoms and one or more heteroatoms in the parent chain (“hetero C _1-7 alkyl”). In some embodiments, the heteroalkyl group is a saturated group having 1 to 6 carbon atoms and one or more heteroatoms in the parent chain (“hetero C _1-6 alkyl”). In some embodiments, the heteroalkyl group is a saturated group having 1 to 5 carbon atoms and 1 or 2 heteroatoms in the parent chain (“hetero C _1-5 alkyl”). In some embodiments, the heteroalkyl group is a saturated group having 1 to 4 carbon atoms and 1 or 2 heteroatoms in the parent chain (“hetero C _1-4 alkyl”). In some embodiments, the heteroalkyl group is a saturated group having 1-3 carbon atoms and 1 heteroatom in the parent chain (“hetero C _1-3 alkyl”). In some embodiments, the heteroalkyl group is a saturated group having one or two carbon atoms and one heteroatom in the parent chain (“hetero C _1-2 alkyl”). In some embodiments, the heteroalkyl group is a saturated group having one carbon atom and one heteroatom in the parent chain (“hetero C1 alkyl”). In some embodiments, the heteroalkyl group is a saturated group having 2 to 6 carbon atoms and 1 or 2 heteroatoms in the parent chain (“hetero C _2-6 alkyl”). Unless otherwise specified, each of the heteroalkyl groups is independently unsubstituted (“unsubstituted heteroalkyl”) or substituted with one or more substituents (“unsubstituted heteroalkyl”). "Substituted heteroalkyl"). In some embodiments, the heteroalkyl group is an unsubstituted hetero C _1-10 alkyl. In some embodiments, the heteroalkyl group is a substituted hetero C _1-10 alkyl.

）は、（Ｅ）−または（Ｚ）−二重結合であってよい。 As used herein, "alkenyl" refers to 2 to 10 carbon atoms and one or more carbon-carbon double bonds (eg, 1, 2, 3, or 4). Refers to a linear or branched hydrocarbon group radical having a double bond). In some embodiments, the alkenyl group has 2-9 carbon atoms (“C _2-9 alkenyl”). In some embodiments, the alkenyl group has 2-8 carbon atoms (“C _2-8 alkenyl”). In some embodiments, the alkenyl group has 2-7 carbon atoms (“C _2-7 alkenyl”). In some embodiments, the alkenyl group has 2 to 6 carbon atoms (“C _2-6 alkenyl”). In some embodiments, the alkenyl group has 2-5 carbon atoms (“C _2-5 alkenyl”). In some embodiments, the alkenyl group has 2-4 carbon atoms (“C _2-4 alkenyl”). In some embodiments, the alkenyl group has 2-3 carbon atoms (“C _2-3 alkenyl”). In some embodiments, the alkenyl group has two carbon atoms (“C ₂ alkenyl”). One or more carbon-carbon double bonds may be internal (as in 2-butenyl) or terminal (as in 1-butenyl). _{Examples of C2-4} alkenyl groups are ethenyl (C ₂ ), 1-propenyl (C ₃ ), 2-propenyl (C ₃ ), 1-butenyl (C ₄ ), 2-butenyl (C ₄ ), butadienyl (C 4). C ₄ ) and the like can be mentioned. Examples of the C _2-6 alkenyl group include the aforementioned C _2-4 alkenyl group, as well as pentenyl (C ₅ ), pentadienyl (C ₅ ), hexenyl (C ₆ ) and the like. Further examples of alkenyl include heptenyl (C ₇ ), octenyl (C ₈ ), octatrienyl (C ₈ ) and the like. Unless otherwise specified, each alkenyl group is independently unsubstituted (“unsubstituted alkenyl”) or substituted with one or more substituents (“substitution”). Alkenyl "). In some embodiments, the alkenyl group is an unsubstituted C _2-10 alkenyl. In some embodiments, the alkenyl group is a substituted C _2-10 alkenyl. For alkenyl groups, C = C double bonds for which stereochemistry has not been specified (eg-CH = CHCH ₃ or

) May be a (E) -or (Z) -double bond.

As used herein, a "heteroalkenyl" is an alkenyl group as defined herein, in the parent chain (ie, inserted between adjacent carbon atoms in the parent chain). And / or at least one heteroatom selected from oxygen, nitrogen or sulfur (eg, one, two, three or four heteroatoms) located at one or more ends of the parent chain. ) Is further included. In some embodiments, a heteroalkenyl group refers to a group having 2 to 10 carbon atoms, at least one double bond, and one or more heteroatoms in the parent chain (“hetero C _{2”). -10} alkenyl "). In some embodiments, the heteroalkenyl group has 2-9 carbon atoms, at least one double bond, and one or more heteroatoms in the parent chain (“hetero C _2-9 alkenyl”). ). In some embodiments, the heteroalkenyl group has 2 to 8 carbon atoms, at least one double bond, and one or more heteroatoms in the parent chain (“hetero C _2-8 alkenyl”). ). In some embodiments, the heteroalkenyl group has 2-7 carbon atoms, at least one double bond, and one or more heteroatoms in the parent chain (“hetero C _2-7 alkenyl”). ). In some embodiments, the heteroalkenyl group has 2 to 6 carbon atoms, at least one double bond, and one or more heteroatoms in the parent chain (“hetero C _2-6 alkenyl”). ). In some embodiments, the heteroalkenyl group has 2-5 carbon atoms, at least one double bond, and 1 or 2 heteroatoms in the parent chain (“hetero C _2-5 alkenyl”). .. In some embodiments, the heteroalkenyl group has 2-4 carbon atoms, at least one double bond, and one or two heteroatoms in the parent chain (“hetero C _2-4 alkenyl”). .. In some embodiments, the heteroalkenyl group has 2-3 carbon atoms, at least one double bond, and one heteroatom in the parent chain (“hetero C _2-3 alkenyl”). In some embodiments, the heteroalkenyl group has 2 to 6 carbon atoms, at least one double bond, and one or two heteroatoms in the parent chain (“hetero C _2-6 alkenyl”). .. Unless otherwise specified, each of the heteroalkenyl groups is independently unsubstituted (“unsubstituted heteroalkenyl”) or substituted with one or more substituents (“unsubstituted heteroalkenyl”). "Substituted heteroalkenyl"). In some embodiments, the heteroalkenyl group is an unsubstituted heteroC _2-10 alkenyl. In some embodiments, the heteroalkenyl group is a substituted hetero C _2-10 alkenyl.

As used herein, "alkynyl" is defined as 2 to 10 carbon atoms and one or more carbon-carbon triple bonds (eg, one, two, three or four triple bonds). ) Refers to a linear or branched hydrocarbon group radical (“C _2-10 alkynyl”). In some embodiments, the alkynyl group has 2-9 carbon atoms (“C _2-9 alkynyl”). In some embodiments, the alkynyl group has 2-8 carbon atoms (“C _2-8 alkynyl”). In some embodiments, the alkynyl group has 2-7 carbon atoms (“C _2-7 alkynyl”). In some embodiments, the alkynyl group has 2 to 6 carbon atoms (“C _2-6 alkynyl”). In some embodiments, the alkynyl group has 2-5 carbon atoms (“C _2-5 alkynyl”). In some embodiments, the alkynyl group has 2-4 carbon atoms (“C _2-4 alkynyl”). In some embodiments, the alkynyl group has 2-3 carbon atoms (“C _2-3 alkynyl”). In some embodiments, the alkynyl group has two carbon atoms (“C ₂ alkynyl”). One or more carbon-carbon triple bonds may be internal (eg in 2-butynyl) or terminal (eg in 1-butynyl). Examples of C _2-4 alkynyl groups are, without limitation, ethynyl (C ₂ ), 1-propynyl (C ₃ ), 2-propynyl (C ₃ ), 1-butynyl (C ₄ ), 2-butynyl (C). ₄ ) and the like. Examples of the C _2-6 alkynyl group include the above-mentioned C _2-4 alkynyl group, pentynyl (C ₅ ), hexynyl (C ₆ ) and the like. Unless otherwise specified, each alkynyl group is independently unsubstituted (“unsubstituted alkynyl”) or substituted with one or more substituents (“substitution”). Alkyne "). In some embodiments, the alkynyl group is an unsubstituted C _2-10 alkynyl. In some embodiments, the alkynyl group is a substituted C _2-10 alkynyl.

As used herein, a "heteroalkynyl" is an alkynyl group as defined herein, in the parent chain (ie, between adjacent carbon atoms in the parent chain) and / or. At least one heteroatom selected from oxygen, nitrogen or sulfur (eg, one, two, three or four heteroatoms) located at one or more ends of the parent chain is further added. Refers to those that include. In some embodiments, a heteroalkynyl group refers to a group having 2 to 10 carbon atoms, at least one triple bond, and one or more heteroatoms in the parent chain (“hetero C _{2-”). 10} alkynyl "). In some embodiments, the heteroalkynyl group has 2-9 carbon atoms, at least one triple bond, and one or more heteroatoms in the parent chain (“hetero C _2-9 alkynyl”). .. In some embodiments, the heteroalkynyl group has 2 to 8 carbon atoms, at least one triple bond, and one or more heteroatoms in the parent chain (“hetero C _2-8 alkynyl”). .. In some embodiments, the heteroalkynyl group has 2 to 7 carbon atoms, at least one triple bond, and one or more heteroatoms in the parent chain (“hetero C _2-7 alkynyl”). .. In some embodiments, the heteroalkynyl group has 2 to 6 carbon atoms, at least one triple bond, and one or more heteroatoms in the parent chain (“hetero C _2-6 alkynyl”). .. In some embodiments, the heteroalkynyl group has 2-5 carbon atoms, at least one triple bond, and 1 or 2 heteroatoms in the parent chain (“hetero C _2-5 alkynyl”). In some embodiments, the heteroalkynyl group has 2 to 4 carbon atoms, at least one triple bond, and one or two heteroatoms in the parent chain (“hetero C _2-4 alkynyl”). In some embodiments, the heteroalkynyl group has a few carbon atoms, at least one triple bond, and one heteroatom in the parent chain (“hetero C _2-3 alkynyl”). In some embodiments, the heteroalkynyl group has 2 to 6 carbon atoms, at least one triple bond, and one or two heteroatoms in the parent chain (“hetero C _2-6 alkynyl”). Unless otherwise specified, each of the heteroalkynyl groups is independently unsubstituted (“unsubstituted heteroalkynyl”) or substituted with one or more substituents (“unsubstituted heteroalkynyl”). "Substituted heteroalkynyl"). In some embodiments, the heteroalkynyl group is an unsubstituted heteroC _2-10 alkynyl. In some embodiments, the heteroalkynyl group is a substituted hetero C _2-10 alkynyl.

As used herein, "carbocyclyl" or "carbocyclic" refers to a non-aromatic ring system _{consisting of 3 to 14 intracyclic carbon atoms ("C 3-14 carbocyclyl") and zero heteroatoms.} Refers to the radical of the non-aromatic cyclic hydrocarbon group contained therein. In some embodiments, the carbocyclyl group has _3-10 intracyclical carbon atoms (“C 3-10 carbocyclyl”). In some embodiments, the carbocyclyl group has _3-8 intracyclical carbon atoms (“C 3-8 carbocyclyl”). In some embodiments, the carbocyclyl group has _3-7 intracyclical carbon atoms (“C 3-7 carbocyclyl”). In some embodiments, the carbocyclyl group has _3-6 intracyclical carbon atoms (“C 3-6 carbocyclyl”). In some embodiments, the carbocyclyl group has _4-6 intracyclical carbon atoms (“C 4-6 carbocyclyl”). In some embodiments, the carbocyclyl group has _5-6 intracyclical carbon atoms (“C 5-6 carbocyclyl”). In some embodiments, the carbocyclyl group has _5-10 intracyclical carbon atoms (“C 5-10 carbocyclyl”). Exemplary C _3-6 carbocyclyl groups include, without limitation, cyclopropyl (C ₃ ), cyclopropenel (C ₃ ), cyclobutyl (C ₄ ), cyclobutenyl (C ₄ ), cyclopentyl (C ₅ ), cyclo. Examples thereof include pentenyl (C ₅ ), cyclohexyl (C ₆ ), cyclohexenyl (C ₆ ), cyclohexadienyl (C ₆ ) and the like. Exemplary _{C 3-8} carbocyclyl groups include, without limitation, _{C 3-6} carbocyclyl group above and cycloheptyl _(C 7),, cycloheptenyl _(C 7), cycloheptadienyl _(C 7), cyclohepta Trienyl (C ₇ ), cyclooctyl (C ₈ ), cyclooctenyllu (C ₈ ), bicyclo [2.2.1] heptanyl (C ₇ ), bicyclo [2.2.2] octanyl (C ₈ ) And so on. Exemplary C _3-10 carbocyclyl groups include, without limitation, the aforementioned C _3-8 carbocyclyl groups, as well as cyclononyl (C ₉ ), cyclononenyl (C ₉ ), cyclodecyl (C ₁₀ ), _{cyclodecenyl (C 10} ), Examples thereof include octahydro-1H-indenyl (C ₉ ), decahydronaphthalenyl (C ₁₀ ), spiro [4.5] decanyl (C ₁₀ ) and the like. In some embodiments, the carbocyclyl group is monocyclic (“monocyclic carbocyclyl”) or polycyclic (eg, bicyclic (“bicyclic carbocyclyl”)) or tricyclic (eg, bicyclic carbocyclyl) or tricyclic (eg, bicyclic carbocyclyl) or tricyclic (eg, bicyclic carbocyclyl) or tricyclic (eg. It may be any of (including condensation, cross-linking or spiro ring systems) such as "tricyclic carbocyclyl") and may contain one or more carbon-carbon double or triple bonds, even if saturated. But it may be. "Carbocyclyl" also includes a ring system in which the carbocyclyl ring as defined above is condensed with one or more aryl or heteroaryl groups, wherein the bonding point is on the carbocyclyl ring. In, the carbon number continues to indicate the carbon number in the carbocyclic ring system. Unless otherwise specified, each of the carbocyclyl groups is independently unsubstituted (“unsubstituted carbocyclyl”) or substituted with one or more substituents (“substitution”). Carbocyclyl "). In some embodiments, the carbocyclyl group is an unsubstituted C _3-14 carbocyclyl. In some embodiments, the carbocyclyl group is a substituted C _3-14 carbocyclyl.
In some embodiments, the "carbocyclyl" is a monocyclic saturated carbocyclyl group having _{3 to 14} intracyclic carbon atoms ("C 3-14 cycloalkyl"). In some embodiments, the cycloalkyl group has 3-10 intracyclical carbon atoms (“C _3-10 cycloalkyl”). In some embodiments, the cycloalkyl group has 3-8 intracyclical carbon atoms (“C _3-8 cycloalkyl”). In some embodiments, the cycloalkyl group has 3 to 6 intracyclical carbon atoms (“C _3-6 cycloalkyl”). In some embodiments, the cycloalkyl group has 4-6 intracyclical carbon atoms (“C _4-6 cycloalkyl”). In some embodiments, the cycloalkyl group has 5-6 intracyclical carbon atoms (“C _5-6 cycloalkyl”). In some embodiments, the cycloalkyl group has 5-10 intracyclical carbon atoms (“C _5-10 cycloalkyl”). Examples of C _5-6 cycloalkyl groups include cyclopentyl (C ₅ ) and cyclohexyl (C ₅ ). Examples of C _3-6 cycloalkyl groups include the aforementioned C _5-6 cycloalkyl groups, as well as cyclopropyl (C ₃ ) and cyclobutyl (C ₄ ). Examples of C _3-8 cycloalkyl groups include the aforementioned C _3-6 cycloalkyl groups, as well as cycloheptyl (C ₇ ) and cyclooctyl (C ₈ ). Unless otherwise specified, each of the cycloalkyl groups is independently unsubstituted (“unsubstituted cycloalkyl”) or substituted with one or more substituents (“unsubstituted cycloalkyl”). "Substituted cycloalkyl"). In some embodiments, the cycloalkyl group is an unsubstituted C _3-14 cycloalkyl. In some embodiments, the cycloalkyl group is a substituted C _3-14 cycloalkyl.

As used herein, "heterocyclyl" or "heterocyclic" refers to radicals in a non-aromatic ring system consisting of an intracyclic carbon atom and 1 to 4 ring heteroatoms of 3 to 14 members. Here, each heteroatom is independently selected from nitrogen, oxygen and sulfur (“3-14 member heterocyclyl”). In a heterocyclyl group containing one or more nitrogen atoms, the bond may be a carbon or nitrogen atom, as long as the valence allows. Heterocyclyl groups are fused or crosslinked, such as monocyclic (“monocyclic heterocyclyl”) or polycyclic (eg, bicyclic (“bicyclic heterocyclyl”) or tricyclic (“tricyclic heterocyclyl”)). Or a spiro ring system), which may be saturated or contain one or more carbon-carbon double or triple bonds. Heterocyclyl Polycyclic Ring System One or both rings may contain one or more heteroatoms. A "heterocyclyl" is also a ring system in which a heterocyclyl ring is condensed with one or more carbocyclyl groups as defined above, with a bonding point on either the carbocyclyl or the heterocyclyl ring. Alternatively, a ring system in which a heterocyclyl ring as defined above is condensed with one or more aryls or heteroaryl groups, including one having a bonding point on the heterocyclyl ring, in which case a ring member. The number continues to indicate the number of ring members in the heterocyclyl ring system. Unless otherwise specified, each case of heterocyclyl is independently unsubstituted (“unsubstituted heterocyclyl”) or substituted with one or more substituents (“substituted heterocyclyl”). "). In some embodiments, the heterocyclyl group is an unsubstituted 3- to 14-membered heterocyclyl. In some embodiments, the heterocyclyl group is a substituted 3--14 member heterocyclyl.

In some embodiments, the heterocyclyl group is a 5-10 membered non-aromatic ring system having an intraring carbon atom and 1 to 4 ring heteroatoms, where each heteroatom is independent. Selected from nitrogen, oxygen and sulfur (“5-10 member heterocyclyl”). In some embodiments, the heterocyclyl group is a 5-8 member non-aromatic ring system having an intraring carbon atom and 1 to 4 ring heteroatoms, where each heteroatom is independent. Selected from nitrogen, oxygen and sulfur (“5-8 member heterocyclyl”). In some embodiments, the heterocyclyl group is a 5- to 6-membered non-aromatic ring system having an intra-ring carbon atom and 1 to 4 ring heteroatoms, where each heteroatom is independent. Selected from nitrogen, oxygen and sulfur (“5-6 member heterocyclyl”). In some embodiments, the 5- to 6-membered heterocyclyl has 1-3 ring heteroatoms selected from nitrogen, oxygen and sulfur. In some embodiments, the 5- to 6-membered heterocyclyl has 1-2 ring heteroatoms selected from nitrogen, oxygen and sulfur. In some embodiments, the 5- to 6-membered heterocyclyl has one ring heteroatom selected from nitrogen, oxygen and sulfur.

Exemplary three-membered heterocyclyl groups containing one heteroatom include, but are not limited to, aziridinyl, oxylanyl and tiylanyl. An exemplary 4-membered heterocyclyl group containing a single heteroatom includes, without limitation, azetidinyl, oxetanyl and thietanyl. An exemplary 5-membered heterocyclyl group containing one heteroatom, without limitation, tetrahydrofuranyl, dihydrofuranyl, tetrahydrothiophenyl, dihydrothiophenyl, pyrrolidinyl, dihydropyrrolill and pyrrolyl-2,5-dione. Can be mentioned. Exemplary 5-membered heterocyclyl groups containing two heteroatoms include, without limitation, dioxolanyl, oxathiolanyl and dithiolanyl. Exemplary 5-membered heterocyclyl groups containing 3 heteroatoms include, without limitation, triazolinyl, oxadiazolinyl and thiadiazolinyl. Exemplary 6-membered heterocyclyl groups containing one heteroatom include, but are not limited to, piperidinyl, tetrahydropyranyl, dihydropyridinyl and thianyl. Exemplary 6-membered heterocyclyl groups containing two heteroatoms include, without limitation, piperazinyl, morpholinyl, dithianyl and dioxanyl. An exemplary 6-membered heterocyclyl group containing two heteroatoms includes, without limitation, triadinanyl. Exemplary 7-membered heterocyclyl groups containing a single heteroatom include, without limitation, azepanyl, oxepanyl and thiepanyl. Exemplary 8-membered heterocyclyl groups containing one heteroatom include, without limitation, azocanyl, oxecanyl and thiocanyl. Exemplary bicyclic heterocyclyl groups include, but are not limited to, indolinyl, isoindolinyl, dihydrobenzofuranyl, dihydrobenzothienyl, tetrahydrobenzothienyl, tetrahydrobenzofuranyl, tetrahydroindrill, tetrahydroquinolinyl, tetrahydroisoquinoli. Nyl, Decahydroquinolinyl, Decahydroisoquinolinyl, Octahydrochromenyl, Octahydroisochromenyl, Decahydronaphthylidineyl, Decahydro-1,8-naphthylidineyl, Octahydropyrrole [3,2-b] pyrrole , Indolinyl, phthalimidyl, naphthalimidyl, chromanyl, chromenyl, 1H-benzo [e] [1,4] diazepinyl, 1,4,5,7-tetrahydropyrano [3,4-b] pyrrolyl, 5,6-dihydro- 4H-flo [3,2-b] pyrrole, 6,7-dihydro-5H-flo [3,2-b] pyranyl, 5,7-dihydro-4H-thieno [2,3-c] pyranyl, 2, 3-Dihydro-1H-pyrrolo [2,3-b] pyridinyl, 2,3-dihydroflo [2,3-b] pyridinyl, 4,5,6,7-tetrahydro-1H-pyrrolo [2,3-b] Pyrrodinyl, 4,5,6,7-tetrahydroflo [3,2-c] pyrridinyl, 4,5,6,7-tetrahydrothieno [3,2-b] pyridinyl, 1,2,3,4-tetrahydro- Examples include 1,6-naphthylidineyl.

As used herein, "aryl" is a monocyclic or polycyclic (eg,) monocyclic or polycyclic (eg,) having 6-14 intracyclic carbon atoms and zero heteroatoms provided in an aromatic ring system. Refers to radicals in a bicyclic or tricyclic) 4n + 2 aromatic ring system (eg, having 6, 10 or 14 π electrons shared in a ring array) (“C _6-14 aryl”). In some embodiments, the aryl group has 6 intracyclical carbon atoms (“C ₆ aryl”; eg, phenyl). In some embodiments, the aryl group has 10 intracyclical carbon atoms (“C ₁₀ aryl”; naphthyls such as 1-naphthyl and 2-naphthyl). In some embodiments, the aryl group has 14 _{intracyclical carbon atoms (“C 14} aryl”; eg, anthracyl). "Aryl" also includes a ring system in which an aryl ring as defined above is fused to one or more carbocyclyl or heterocyclyl groups, the radical or bonding point of which is on the aryl ring. In such cases, the number of carbon atoms continues to indicate the number of carbon atoms in the aryl ring system. Unless otherwise specified, each aryl group is independently unsubstituted (“unsubstituted aryl”) or substituted with one or more substituents (“substitution”). Aryl "). In some embodiments, the aryl group is an unsubstituted C _6-14 aryl. In some embodiments, the aryl group is a substituted C _6-14 aryl.

"Aralkyl" is a subset of "alkyl", an alkyl group as defined herein, substituted with an aryl group as defined herein, and the bond point is an alkyl moiety. Refers to what is above.

As used herein, "heteroaryl" is a 5- to 14-membered monocyclic or polycyclic having an intracyclic carbon atom and 1 to 4 ring heteroatoms provided in an aromatic ring system. Refers to radicals of the 4n + 2 aromatic ring system of the formula (eg, bicyclic, tricyclic) (eg, having 6, 10 or 14 π electrons shared in the ring array). Here, each heteroatom is independently selected from nitrogen, oxygen and sulfur ("5-14-membered heteroaryl"). In a heteroaryl group having one or more nitrogen atoms, the bond point may be a carbon or nitrogen atom, as long as the valence allows. Heteroaryl polycyclic ring systems may contain one or more heteroatoms in one or both rings. A "heteroaryl" is a ring system in which a heteroaryl ring as defined above is condensed with one or more carbocyclyls or heterocyclyl groups, the junction of which is on the heteroaryl ring. In such cases, the number of ring members continues to indicate the number of ring members in the heteroaryl ring system. A "heteroaryl" is also a ring system in which a heteroaryl ring as defined above is fused with one or more aryl groups, with a bonding point on either the aryl or the heteroaryl ring. Including some, in such cases, the number of ring members indicates the number of ring members in a fused polycyclic (aryl / heteroaryl) ring system. In a polycyclic heteroaryl group in which one ring does not contain a heteroatom (eg, indolyl, quinolinyl, carbazolyl, etc.), the bond may be on any ring, i.e., a heteroatom (eg, 2-indolyl). ), Or a ring that does not contain a heteroatom (for example, 5-indrill).

In some embodiments, the heteroaryl group is a 5-10 membered aromatic ring system having an intraring carbon atom and 1 to 4 ring heteroatoms provided in the aromatic ring system, wherein each heteroatom is here. Are independently selected from nitrogen, oxygen and sulfur (“5-10 membered heteroaryl”). In some embodiments, the heteroaryl group is a 5- to 8-membered aromatic ring system having an intra-ring carbon atom and 1 to 4 ring heteroatoms provided in the aromatic ring system, wherein each hetero is here. Atoms are independently selected from nitrogen, oxygen and sulfur (“5-8 membered heteroaryls”). In some embodiments, the heteroaryl group is a 5- to 6-membered aromatic ring system having an intra-ring carbon atom and 1 to 4 ring heteroatoms provided in the aromatic ring system, wherein each heteroatom is here. Are independently selected from nitrogen, oxygen and sulfur ("5-6-membered heteroaryl"). In some embodiments, the 5- to 6-membered heteroaryl has 1-3 ring heteroatoms selected from nitrogen, oxygen and sulfur. In some embodiments, the 5- to 6-membered heteroaryl has 1-2 ring heteroatoms selected from nitrogen, oxygen and sulfur. In some embodiments, the 5- to 6-membered heteroaryl has one ring heteroatom selected from nitrogen, oxygen and sulfur. Unless otherwise specified, each of the heteroaryl groups is independently unsubstituted (“unsubstituted heteroaryl”) or substituted with one or more substituents (“unsubstituted heteroaryl”). "Substituted heteroaryl"). In some embodiments, the heteroaryl group is an unsubstituted 5- to 14-membered heteroaryl. In some embodiments, the heteroaryl group is a substituted 5-14 member heteroaryl.

Exemplary 5-membered heteroaryl groups containing one heteroatom include, without limitation, pyrrolyl, furanyl and thiophenyl. Exemplary 5-membered heteroaryl groups containing two heteroatoms include, without limitation, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl and isothiazolyl. Exemplary 5-membered heteroaryl groups containing 3 heteroatoms include, without limitation, triazolyl, oxadiazolyl and thiadiazolyl. An exemplary 5-membered heteroaryl group containing 4 heteroatoms includes, without limitation, tetrazolyl. An exemplary 6-membered heteroaryl group containing one heteroatom includes, without limitation, pyridinyl. Exemplary 6-membered heteroaryl groups containing two heteroatoms include, without limitation, pyridadinyl, pyrimidinyl and pyrazinyl. Exemplary 6-membered heteroaryl groups containing 3 or 4 heteroatoms include, without limitation, triazinyl and tetrazinyl, respectively. Exemplary 7-membered heteroaryl groups containing one heteroatom include, without limitation, azepinyl, oxepynyl and thiepinyl. Exemplary 5,6-bicyclic heteroaryl groups include, but are not limited to, indolyl, isoindrill, indazolyl, benzotriazolyl, benzothiophenyl, isobenzothiophenyl, benzofuranyl, benzoisofuranyl, benzoimidazolyl, benzoxazolyl, Included are benzoisoxazolyl, benzoxaziazolyl, benzothiazolyl, benzoisothiazolyl, benzothiadiazolyl, indridinyl and prynyl. Exemplary 6,6-bicyclic heteroaryl groups include, but are not limited to, naphthyldinyl, pteridinyl, quinolinyl, isoquinolinyl, cinnolinyl, quinoxalinyl, phthalazinyl and quinazolinyl. Exemplary tricyclic heteroaryl groups include, but are not limited to, phenanthyldinyl, dibenzofuranyl, carbazolyl, acridinyl, phenothiazinyl, phenoxadinyl and phenazinyl.

A "heteroaralkyl" is a subset of "alkyl", an alkyl group as defined herein, substituted with a heteroaryl group as defined herein, and a bond point. Refers to what is on the alkyl moiety.

As used herein, the term "partially unsaturated" refers to a ring moiety that contains at least one double or triple bond. The term "partially unsaturated", as defined herein, is intended to include rings with multiple unsaturated sites, but with aromatic groups (eg, aryl or heteroaryl moieties). It is not intended to be included.

As used herein, the term "saturated" refers to a ring moiety that does not contain a double or triple bond, i.e., all rings include a single bond.

Attaching the suffix "en" to the base indicates that the group is a divalent moiety, for example alkylene is the divalent moiety of alkyl, alkenylene is the divalent moiety of alkenyl, and alkynylene is the divalent moiety of alkynyl. It is a divalent moiety, heteroalkylene is a divalent moiety of heteroalkyl, heteroalkenylene is a divalent moiety of heteroalkenyl, heteroalkynylene is a divalent moiety of heteroalkynyl, and carbocyclylene is divalent of carbocyclyl. Heterocyclylene is the divalent portion of heterocyclyl, arylene is the divalent portion of aryl, and heteroarylene is the divalent portion of heteroaryl.

As is apparent from the above, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl and heteroaryl groups as defined herein are optionally substituted in certain embodiments. .. Arbitrarily substituted means a group that may be substituted or unsubstituted (eg, "substituted" or "unsubstituted" alkyl, "substituted" or "unsubstituted" alkenyl, "substituted" or "unsubstituted". "Substituted" alkynyl, "substituted" or "unsubstituted" heteroalkyl, "substituted" or "unsubstituted" heteroalkenyl, "substituted" or "unsubstituted" heteroalkynyl, "substituted" or "unsubstituted" carbocyclyl, "substituted" Alternatively, it refers to a "unsubstituted" heterocyclyl, a "substituted" or "unsubstituted" aryl, or a "substituted" or "unsubstituted" heteroaryl group). In general, the term "substituted" means that at least one hydrogen present in a group is an acceptable substituent, eg, a compound that is stable by substitution (eg, a compound that is stable by substitution, eg, rearrangement, ring). It means that it is substituted with a substituent that produces a compound that does not spontaneously cause a conversion reaction such as conversion, elimination, or other reaction. Unless otherwise indicated, a "substituted" group has a substituent at one or more substitutable positions of the group, where more than one position is substituted in any given structure. , Substituents are the same or different at each position. The term "substituted" includes any of the substituents described herein that are intended to include substitutions of organic compounds with all acceptable substituents and result in the formation of stable compounds. The present invention contemplates any and all such combinations in order to reach stable compounds. For the purposes of the present invention, heteroatoms such as nitrogen are hydrogen substituents and / or any suitable substitutions described herein that satisfy the valence of the heteroatom and result in the formation of stable moieties. It may have a group.

Exemplary carbon atom substituents include, but are not limited to, halogen, -CN, -NO ₂ , -N ₃ , -SO ₂ H, -SO ₃ H, -OH, -OR ^aa , -ON (R ^bb ) _{2. ^{, -N (R bb) 2,}} -N (R bb) 3 + X -, -N (OR cc) R bb, -SH, -SR aa, -SSR cc, -C (= O) R aa, - CO ₂ H, -CHO, -C (OR ^cc ) ₂ , -CO ₂ R ^aa , -OC (= O) R ^aa , -OCO ₂ R ^aa , -C (= O) N (R ^bb ) ₂ ,- OC (= O) N (R ^bb ) ₂ , -NR ^bb C (= O) R ^aa , -NR ^bb CO ₂ R ^aa , -NR ^bb C (= O) N (R ^bb ) ₂ , -C (= NR ^bb ) R ^aa , -C (= NR ^bb ) OR ^aa , -OC (= NR ^bb ) R ^aa , -OC (= NR ^bb ) OR ^aa , -C (= NR ^bb ) N (R ^bb ) ₂ , -OC (= NR ^bb ) N (R ^bb ) ₂ , -NR ^bb C (= NR ^bb ) N (R ^bb ) ₂ , -C (= O) NR ^bb SO ₂ R ^aa , -NR ^bb SO ₂ R ^aa , -SO ₂ N (R ^bb ) ₂ , -SO ₂ R ^aa , -SO ₂ OR ^aa , -OSO ₂ R ^aa , -S (= O) R ^aa , -OS (= O) R ^aa , -Si ( R ^aa ) ₃ , -OSi (R ^aa ) ₃ , -C (= S) N (R ^bb ) ₂ , -C (= O) SR ^aa , -C (= S) SR ^aa , -SC (= S) SR ^aa , -SC (= O) SR ^aa , -OC (= O) SR ^aa , -SC (= O) OR ^aa , -SC (= O) R ^aa , -P (= O) ₂ R ^aa ,- OP (= O) ₂ R ^aa , -P (= O) (R ^aa ) ₂ , -OP (= O) (R ^aa ) ₂ , -OP (= O) (OR ^cc ) ₂ , -P (= O) ) ₂ N (R ^bb ) ₂ , -OP (= O) ₂ N (R ^bb ) ₂ , -P (= O) (NR ^bb ) ₂ , -OP (= O) (NR ^bb ) ₂ , -NR ^bb P (= O) (OR ^cc ) ₂ , -NR ^bb P (= O) (NR ^bb ) ₂ , -P (R ^cc ) ₂ , -P (R ^cc ) ₃ , -OP (R ^cc ) ₂ ,- OP (R) ^cc ) ₃ , -B (R ^aa ) ₂ , -B (OR ^cc ) ₂ , -BR ^aa (OR ^cc ), C _1-10 alkyl, C _1-10 perhaloalkyl, C _2-10 alkyne, C _{2- 10} alkynyl, hetero C _1-10 alkyl, hetero C _2-10 alkenyl, hetero C _2-10 alkynyl, C _3-10 carbocyclyl, 3-14 member heterocyclyl, C _6-14 aryl, and 5-14 member heteroaryl Here, each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl and heteroaryl are independently 0, 1, 2, 3, 4 or 5 Rs. Substituted with an ^{dd group;}
Alternatively, the two geominal hydrogens on the carbon atom have groups = O, = S, = NN (R ^bb ) ₂ , = NNR ^bb C (= O) R ^aa , = NNR ^bb C (= O) OR ^aa. , = NNR ^bb S (= O) ₂ R ^aa , = NR ^bb or = NOR ^cc ;
In ^{each case of Raa} , independently, C _1-10 alkyl, C _1-10 perhaloalkyl, C _2-10 alkenyl, C _2-10 alkynyl, hetero C _1-10 alkyl, hetero C _2-10 alkenyl. , hetero _{C 2-10 alkynyl, C 3-10} carbocyclyl, 3-14 membered _{heterocyclyl, C 6-14} or aryl, and 5-14 membered heteroaryl, or two ^{R aa} groups, is coupled Form a 3- to 14-membered heterocyclyl or 5- to 14-membered heteroaryl ring, where the respective alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl and heteroaryl are independent. , 0, 1, 2, 3, 4 or 5 R ^dd groups;
In ^{each case of R bb} , independently, hydrogen, -OH, -OR ^aa , -N (R ^cc ) ₂ , -CN, -C (= O) R ^aa , -C (= O) N (R) ^cc ) ₂ , -CO ₂ R ^aa , -SO ₂ R ^aa , -C (= NR ^cc ) OR ^aa , -C (= NR ^cc ) N (R ^cc ) ₂ , -SO ₂ N (R ^cc ) ₂ , -SO ₂ R ^cc , -SO ₂ OR ^cc , -SOR ^aa , -C (= S) N (R ^cc ) ₂ , -C (= O) SR ^cc , -C (= S) SR ^cc , -P ( = O) ₂ R ^aa , -P (= O) (R ^aa ) ₂ , -P (= O) ₂ N (R ^cc ) ₂ , -P (= O) (NR ^cc ) ₂ , C _1-10 alkyl , C _1-10 perhaloalkyl, C _2-10 alkynyl, C _2-10 alkynyl, hetero C _1-10 alkyl, hetero C _2-10 alkenyl, hetero C _2-10 alkynyl, C _3-10 carbocyclyl, 3-14 membered _{heterocyclyl, C 6-14} aryl, or two ^{R bb} groups or selected, and the 5-14 membered heteroaryl is connected forming a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring , Where each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl and heteroaryl are independently 0, 1, 2, 3, 4 or 5 R ^dd groups. Replaced by;
In ^{each case of R cc} , independently, hydrogen, C _1-10 alkyl, C _1-10 perhaloalkyl, C _2-10 alkenyl, C _2-10 alkynyl, hetero C _1-10 alkyl, hetero C _{2- Selected from 10} alkenyl, hetero C _2-10 alkynyl, C _3-10 carbocyclyl, 3-14 member heterocyclyl, C _6-14 aryl, and 5-14 member heteroaryl, or two R ^cc groups They are linked to form a 3- to 14-membered heterocyclyl or 5- to 14-membered heteroaryl ring, where the respective alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl and heteroaryl are independent. Then, it is substituted with 0, 1, 2, 3, 4 or 5 ^{Rdd groups;}
In ^{each case of R dd} , independently, halogen, -CN, -NO ₂ , -N ₃ , -SO ₂ H, -SO ₃ H, -OH, -OR ^ee , -ON (Rff) ₂ ,- ^{_{N (Rff) 2, -N (}} Rff) 3 + X -, -N (OR ee) Rff, -SH, -SR ee, -SSR ee, -C (= O) R ee, -CO 2 H, - CO ₂ R ^ee , -OC (= O) R ^ee , -OCO ₂ R ^ee , -C (= O) N (R ^ff ) ₂ , -OC (= O) N (R ^ff ) ₂ , -NR ^ff C (= O) R ^ee , -NR ^ff CO ₂ R ^ee , -NR ^ff C (= O) N (R ^ff ) ₂ , -C (= NR ^ff ) OR ^ee , -OC (= NR ^ff ) R ^ee , -OC (= NR ^ff ) OR ^ee , -C (= NR ^ff ) N (R ^ff ) ₂ , -OC (= NR ^ff ) N (R ^ff ) ₂ , -NR ^ff C (= NR ^ff ) N (R) ^ff ) ₂ , -NR ^ff SO ₂ R ^ee , -SO ₂ N (R ^ff ) ₂ , -SO ₂ R ^ee , -SO ₂ OR ^ee , -OSO ₂ R ^ee , -S (= O) R ^ee ,- Si ( ^Ree ) ₃ , -OSi ( ^Ree ) ₃ , -C (= S) N (R ^ff ) ₂ , -C (= O) SR ^ee , -C (= S) SR ^ee , -SC (= S) SR ^ee , -P (= O) ₂ R ^ee , -P (= O) ( ^Ree ) ₂ , -OP (= O) ( ^Ree ) ₂ , -OP (= O) (OR ^ee ) ₂ , C _1-6 Alkyne, C _1-6 Perhaloalkyl, C _2-6 Alkyne, C _2-6 Alkyne, Hetero C _1-6 Alkyne, Hetero C _2-6 Alkyne, Hetero C _2-6 Alkyne, C _{3- Selected from 10} carbocyclyls, 3-10 membered heterocyclyls, C _6-10 aryls, 5-10 membered heteroaryls, where each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl and Heteroaryls are independently substituted with 0, 1, 2, 3, 4 or 5 R ^gg groups, or 2 Geminal R ^dd substituents are linked and = O or = S may be formed;
In ^{each case of Ree} , independently, C _1-6 alkyl, C _1-6 perhaloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, hetero C _1-6 alkyl, hetero C _2-6 alkenyl. , Hetero C _2-6 alkynyl, C _3-10 carbocyclyl, C _6-10 aryl, 3-10 member heterocyclyl, and 3-10 member heteroaryl, where the respective alkyl, alkenyl, alkynyl, heteroalkyl, Heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl and heteroaryl are independently substituted with ^{0, 1, 2, 3, 4 or 5 Rgg groups;}
In ^{each case of R ff} , hydrogen, C _1-6 alkyl, C _1-6 perhaloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, hetero C _1-6 alkyl, hetero C _{2- Selected from 6} alkenyl, hetero C _2-6 alkynyl, C _3-10 carbocyclyl, 3-10 member heterocyclyl, C _6-10 aryl, and 5-10 member heteroaryl, or two R ^ff groups They are linked to form a 3- to 10-membered heterocyclyl or 5- to 10-membered heteroaryl ring, where the respective alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl and heteroaryl are independent. Then, it is substituted with 0, 1, 2, 3, 4 or 5 R ^{gg groups; and in each case of R gg} , halogen, -CN, -NO ₂ , -N ₃ ,- SO ₂ H, -SO ₃ H, -OH, -OC _1-6 alkyl, -ON (C _1-6 alkyl) ₂ , -N (C _1-6 alkyl) ₂ , -N (C _1-6 alkyl) ^{_{3 + X -, -NH (C}} 1-6 ^{_{alkyl) 2 + X -, -NH 2}} (C 1-6 ^{_{alkyl) + X -, -NH 3 +}} X -, -N (OC 1-6 alkyl) ( C _1-6 alkyl), -N (OH) (C _1-6 alkyl), -NH (OH), -SH _{, -SC 1-6} alkyl, -SS (C _1-6 alkyl), -C (= O) (C _1-6 alkyl), _{-CO 2} H, -CO ₂ (C _1-6 alkyl), -OC (= O) (C _1-6 alkyl), -OCO ₂ (C _1-6 alkyl) , -C (= O) NH ₂ , -C (= O) N (C _1-6 alkyl) ₂ , -OC (= O) NH (C _1-6 alkyl), -NHC (= O) (C _{1) -6} alkyl), -N (C _1-6 alkyl) C (= O) (C _1-6 alkyl), -NHCO ₂ (C _1-6 alkyl), -NHC (= O) N (C _{1-6) Alkyne 2} , -NHC (= O) NH (C _1-6 alkyl), -NHC (= O) NH ₂ , -C (= NH) O (C _1-6 alkyl), -OC (= NH) ( C _1-6 alkyl), -OC (= NH) OC _1-6 alkyl, -C (= NH) N (C _1-6 alkyl) ₂ , -C (= NH) NH (C _1-6 alkyl), -C (= NH) NH ₂ , -OC (= N) H) N (C _1-6 alkyl) ₂ , -OC (NH) NH (C _1-6 alkyl), -OC (NH) NH ₂ , -NHC (NH) N (C _1-6 alkyl) ₂ ,- NHC (= NH) NH ₂ , -NHSO ₂ (C _1-6 alkyl), -SO ₂ N (C _1-6 alkyl) ₂ , -SO ₂ NH (C _1-6 alkyl), -SO ₂ NH ₂ , -SO ₂ C _{1-6 alkyl,} -SO _{2 OC 1-6} alkyl, -OSO ₂ C _1-6 alkyl, _{-SOC 1-6} alkyl, -Si _{(C 1-6 alkyl)} 3, -OSi _{(C 1 -6} alkyl) ₃ , -C (= S) N (C _1-6 alkyl) ₂ , C (= S) NH (C _1-6 alkyl), C (= S) NH ₂ , -C (= O) S (C _1-6 alkyl), -C (= S) SC _1-6 alkyl, -SC (= S) SC _1-6 alkyl, -P (= O) ₂ (C _1-6 alkyl), -P (= O) (C _1-6 alkyl) ₂ , -OP (= O) (C _1-6 alkyl) ₂ , -OP (= O) (OC _1-6 alkyl) ₂ , C _1-6 alkyl, C _1-6 perhaloalkyl, C _2-6 alkynyl, C _2-6 alkynyl, hetero C _1-6 alkyl, hetero C _2-6 alkenyl, hetero C _2-6 alkynyl, C _3-10 carbocyclyl, C _6-10 aryl Is it a 3- to 10-membered heterocyclyl, a 5- to 10-membered heteroaryl; or two Geminal ^Rgg substituents may be linked to form = O or = S; where X ^-Is a counter ion.

As used herein, the term "halo" or "halogen" means fluorine (fluoro, -F), chlorine (chloro, -Cl), bromine (bromo, -Br), or iodine (iodine, -I). ).

In some embodiments, the substituent present on the nitrogen atom is a nitrogen protecting group (also referred to herein as an "amino protecting group"). Nitrogen protective groups include, but are not limited to -OH, -OR ^aa , -N (R ^cc ) ₂ , -C (= O) R ^aa , -C (= O) N (R ^cc ) ₂ , -CO ₂ R. ^aa , -SO ₂ R ^aa , -C (= NR ^cc ) R ^aa , -C (= NR ^cc ) OR ^aa , -C (= NR ^cc ) N (R ^cc ) ₂ , -SO ₂ N (R ^cc ) ₂ , -SO ₂ R ^cc , -SO ₂ OR ^cc , -SOR ^aa , -C (= S) N (R ^cc ) ₂ , -C (= O) SR ^cc , -C (= S) SR ^cc , C _1-10 alkyl (eg alkyl, aralkyl, heteroaralkyl), C _2-10 alkenyl, C _2-10 alkynyl, C _1-10 heteroalkyl, C _2-10 heteroalkenyl, C _2-10 heteroalkynyl, C _{3- 10} Carbocyclyls, 3-14 membered heterocyclyls, C _6-14 aryl, and 5-14 membered heteroaryl groups are mentioned, wherein the respective alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, Alkynes, aryls and heteroaryls are independently substituted with 0, 1, 2, 3, 4 or 5 R ^dd groups, where R ^aa , R ^bb , R ^cc and R ^dd are herein. As described in. Nitrogen protecting groups are well known in the art and are described in detail in the Protecting Groups in Organic Synthesis (TW Greene and PGM Wuts, 3rd Edition, John Wiley & Sons, 1999), which is incorporated herein by reference. Including what is done.

For example, the nitrogen protecting group such as an amide group (e.g., ^{-C (= O) R aa)} , but are not limited to, formamide, acetamide, chloroacetamide, trichloro acetamide, trifluoroacetamide, phenyl acetamide, 3-phenyl Propanamide, picolinamide, 3-pyridylcarboxamide, N-benzoylphenylalanyl derivative, benzamide, p-phenylbenzamide, o-nitrophenylacetamide, o-nitrophenoxyacetamide, acetoacetamide, (N'-dithiobenzyl) Oxyacylamino) acetamide, 3- (p-hydroxyphenyl) propanamide, 3- (o-nitrophenyl) propanamide, 2-methyl-2- (o-nitrophenoxy) propanamide, 2-methyl-2- ( o-phenylazophenoxy) propanamide, 4-chlorobutaneamide, 3-methyl-3-nitrobutaneamide, o-nitrocinnamide, N-acetylmethionine derivative, o-nitrobenzamide and o- (benzoyloxymethyl) benzamide. Be done.

As nitrogen protecting groups such as carbamate groups (eg, -C (= O) OR ^aa ), but not limited to methyl carbamate, ethyl carbamate, 9-fluorenyl methyl carbamate (Fmoc), 9- (2-sulfo) fluore Nylmethylcarbamate, 9- (2,7-dibromo) fluorenylmethylcarbamate, 2,7-di-t-butyl- [9- (10,10-dioxo-10,10,10,10-tetrahydrothioxane) Chill] Methyl carbamate (DBD-Tmoc), 4-methoxyphenacil carbamate (Phenoc), 2,2,2-trichloroethyl carbamate (Troc), 2-trimethylsilylethyl carbamate (Teoc), 2-phenylethyl carbamate (hZ) ), 1- (1-adamantyl) -1-methylethylcarbamate (Adpoc), 1,1-dimethyl-2-haloethylcarbamate, 1,1-dimethyl-2,2-dibromoethylcarbamate (DB-t-BOC) ), 1,1-dimethyl-2,2,2-trichloroethyl carbamate (TCBOC), 1-methyl-1- (4-biphenylyl) ethyl carbamate (Bpoc), 1- (3,5-di-t-butyl) Phenyl) -1-methylethylcarbamate (t-Bumeoc), 2- (2'-and 4'-pyridyl) ethylcarbamate (Pyoc), 2- (N, N-dicyclohexylcarboxamide) ethylcarbamate, t-butylcarbamate (t-butylcarbamate) BOC), 1-adamantyl carbamate (Adoc), vinyl carbamate (Voc), allyl carbamate (Alloc), 1-isopropylallyl carbamate (Ipaoc), cinnamyl carbamate (Coc), 4-nitrocinnamyl carbamate (Noc), 8 -Kinolyl carbamate, N-hydroxypiperidinyl carbamate, alkyldithiocarbamate, benzyl carbamate (Cbz), p-methoxybenzyl carbamate (Moz), p-nitrobenzyl carbamate, p-bromobenzyl carbamate, p-chlorobenzyl carbamate, 2,4-Dichlorobenzylcarbamate, 4-methylsulfinylbenzylcarbamate (Msz), 9-anthrylmethylcarbamate, diphenylmethylcarbamate, 2-methylthioethylcarbamate, 2-methylsulfonylethylcarbamate, 2- (p-toluenesulfonyl) Ethyl carbamate, [2 -(1,3-Dithianyl)] Methyl carbamate (Dmoc), 4-methylthiophenyl carbamate (Mtpc), 2,4-dimethylthiophenyl carbamate (Bmpc), 2-phosphonioethyl carbamate (Peoc), 2-triphenyl Phosphonioisopropylcarbamate (Ppoc), 1,1-dimethyl-2-cyanoethylcarbamate, m-chloro-p-acyloxybenzylcarbamate, p- (dihydroxyboryl) benzylcarbamate, 5-benzoisoxazolylmethylcarbamate, 2- (Trifluoromethyl) -6-chromonyl methyl carbamate (Tcroc), m-nitrophenyl carbamate, 3,5-dimethoxybenzyl carbamate, o-nitrobenzyl carbamate, 3,4-dimethoxy-6-nitrobenzyl carbamate, phenyl ( o-nitrophenyl) methyl carbamate, t-amyl carbamate, S-benzylthio carbamate, p-cyanobenzyl carbamate, cyclobutyl carbamate, cyclohexyl carbamate, cyclopentyl carbamate, cyclopropyl methyl carbamate, p-decyloxybenzyl carbamate, 2,2 -Dimethoxyacylvinylcarbamate, o- (N, N-dimethylcarboxamide) benzylcarbamate, 1,1-dimethyl-3- (N, N-dimethylcarboxamide) propylcarbamate, 1,1-dimethylpropynylcarbamate, di (2-) Pyridyl) Methyl Carbamate, 2-Franyl Methyl Carbamate, 2-Iodoethyl Carbamate, Isobornyl Carbamate, Isobutyl Carbamate, Isonicotinyl Carbamate, p- (p'-methoxyphenylazo) benzyl Carbamate, 1-Methylcyclobutyl Carbamate , 1-Methylcyclohexylcarbamate, 1-methyl-1-cyclopropylmethylcarbamate, 1-methyl-1- (3,5-dimethoxyphenyl) ethylcarbamate, 1-methyl-1- (p-phenylazophenyl) ethylcarbamate , 1-Methyl-1-phenylethyl carbamate, 1-methyl-1- (4-pyridyl) ethyl carbamate, phenyl carbamate, p- (phenylazo) benzyl carbamate, 2,4,6-tri-t-butylphenyl carbamate, 4- (trimethylammonium) benzyl carbamate, as well as 2,4,6-trimethylbenzyl carbamate To be mentioned.

As a nitrogen-protecting group such as a sulfonamide group (eg, -S (= O) ₂ ^Raa ), but not limited to, p-toluenesulfonamide (Ts), benzenesulfonamide, 2,3,6-trimethyl-4-methoxy. Benzenesulfonamide (Mtr), 2,4,6-trimethoxybenzenesulfonamide (Mtb), 2,6-dimethyl-4-methoxybenzenesulfonamide (Pme), 2,3,5,6-tetramethyl-4 −methoxybenzenesulfonamide (Mte), 4-methoxybenzenesulfonamide (Mbs), 2,4,6-trimethylbenzenesulfonamide (Mts), 2,6-dimethoxy-4-methylbenzenesulfonamide (iMds), 2 , 2,5,7,8-Pentamethylchroman-6-sulfonamide (Pmc), methanesulfonamide (Ms), β-trimethylsilylethanesulfonamide (SES), 9-anthracene sulfonamide, 4- (4', 8'-Dimethoxynaphthylmethyl) benzenesulfonamide (DNMBS), benzylsulfonamide, trifluoromethylsulfonamide, and phenacylsulfonamide.

Other nitrogen-protecting groups include, but are not limited to, phenothiazinyl- (10) -acyl derivative, N'-p-toluenesulfonylaminoacyl derivative, N'-phenylaminothioacyl derivative, N-benzoylphenylalanyl derivative, N-. Acetylmethionine derivatives, 4,5-diphenyl-3-oxazoline-2-one, N-phthalimide, N-dithiascusinimide (Dts), N-2,3-diphenylmaleimide, N-2,5-dimethylpyrrole, N -1,1,4,4-tetramethyldisilylazacyclopentane adduct (STABASE), 5-substituted 1,3-dimethyl-1,3,5-triazacyclohexane-2-one, 5-substituted 1, 3-Dibenzyl-1,3,5-triazacyclohexane-2-one, 1-substituted 3,5-dinitro-4-pyridone, N-methylamine, N-allylamine, N- [2- (trimethylsilyl) ethoxy] Methylamine (SEM), N-3-acetoxypropylamine, N- (1-isopropyl-4-nitro-2-oxo-3-pyrrolin-3-yl) amine, quaternary ammonium salt, N-benzylamine, N −Di (4-methoxyphenyl) methylamine, N-5-dibenzosverylamine, N-triphenylmethylamine (Tr), N-[(4-methoxyphenyl) diphenylmethyl] amine (MMTr), N-9- Phenylfluorenylamine (PhF), N-2,7-dichloro-9-fluorenylmethyleneamine, N-ferrocenylmethylamino (Fcm), N-2-picorylamino N'-oxide, N-1,1 -Dimethylthiomethyleneamine, N-benzylideneamine, N-p-methoxybenzideneamine, N-diphenylmethyleneamine, N-[(2-pyridyl) mesityl] methyleneamine, N- (N', N'-dimethylaminomethylene ) Amine, N, N'-isopropyridenediamine, Np-nitrobenzylenemine, N-salicylideneamine, N-5-chlorosalicylideneamine, N- (5-chloro-2-hydroxyphenyl) phenyl Methyleneamine, N-cyclohexylideneamine, N- (5,5-dimethyl-3-oxo-1-cyclohexenyl) amine, N-boran derivative, N-diphenylboronic acid derivative, N- [phenyl (pentaacylchrome) -Or tungsten) acyl] amine, N-copper chelate, N-zinc chelate, N-nitroamine, N-nitrosoamine, amine N-oxide, diphenylphosphine amide (Dpp), dimethylthiophosphine amide (Mpt), diphenylthiophosphine amide (Ppt), dialkylphosphoramide, dibenzylphosphoramide, diphenylphosphoramide, benzenesulphenamide , O-Nitrobenzenesulfenamide (Nps), 2,4-dinitrobenzenesulfenamide, pentachlorobenzenesulfenamide, 2-nitro-4-methoxybenzenesulfenamide, triphenylmethylsulfenamide, and 3-nitro Pyridine sulfene amide (Npys) can be mentioned.

In some embodiments, the substituent present on the oxygen atom is an oxygen protecting group (also referred to herein as a "hydroxyl protecting group"). Oxygen protective groups include, but are not limited to -R ^aa , -N (R ^bb ) ₂ , -C (= O) SR ^aa , -C (= O) R ^aa , -CO ₂ R ^aa , -C (= O). ) N (R ^bb ) ₂ , -C (= NR ^bb ) R ^aa , -C (= NR ^bb ) OR ^aa , -C (= NR ^bb ) N (R ^bb ) ₂ , -S (= O) R ^aa , -SO ₂ R ^aa , -Si (R ^aa ) ₃ , -P (R ^cc ) ₂ , -P (R ^cc ) ₃ , -P (= O) ₂ R ^aa , -P (= O) (R ^aa) ) ₂ , -P (= O) (OR ^cc ) ₂ , -P (= O) ₂ N (R ^bb ) ₂ , and -P (= O) (NR ^bb ) ₂ , where R ^aa , R ^bb and R ^cc are as described herein. Oxygen protecting groups are well known in the art and are described in detail in the Protecting Groups in Organic Synthesis (TW Greene and PGM Wuts, 3rd Edition, John Wiley & Sons, 1999), which is incorporated herein by reference. Including things.

Exemplary oxygen protective groups include, but are not limited to, methyl, methoxylmethyl (MOM), methylthiomethyl (MTM), t-butylthiomethyl, (phenyldimethylsilyl) methoxymethyl (SMOM), benzyloxymethyl (BOM), p-methoxybenzyloxymethyl (PMBM), (4-methoxyphenoxy) methyl (p-AOM), guaiacol methyl (GUM), t-butoxymethyl, 4-pentenyloxymethyl (POM), siloxymethyl, 2-methoxyethoxy Methyl (MEM), 2,2,2-trichloroethoxymethyl, bis (2-chloroethoxy) methyl, 2- (trimethylsilyl) ethoxymethyl (SEMOR), tetrahydropyranyl (THP), 3-bromotetrahydropyranyl, tetrahydro Thiopyranyl, 1-methoxycyclohexyl, 4-methoxytetrahydropyranyl (MTHP), 4-methoxytetrahydrothiopyranyl, 4-methoxytetrahydrothiopyranyl S, S-dioxide, 1-[(2-chloro-4- Methyl) phenyl] -4-methoxypiperidin-4-yl (CTMP), 1,4-dioxan-2-yl, tetrahydrofuranyl, tetrahydrothiofuranyl, 2,3,3a, 4,5,6,7,7a -Octahydro-7,8,8-trimethyl-4,7-methanobenzofuran-2-yl, 1-ethoxyethyl, 1- (2-chloroethoxy) ethyl, 1-methyl-1-methoxyethyl, 1-methyl- 1-benzyloxyethyl, 1-methyl-1-benzyloxy-2-fluoroethyl, 2,2,2-trichloroethyl, 2-trimethylsilylethyl, 2- (phenylselenyl) ethyl, t-butyl, allyl, p -Chlorophenyl, p-methoxyphenyl, 2,4-dinitrophenyl, benzyl (Bn), p-methoxybenzyl, 3,4-dimethoxybenzyl, o-nitrobenzyl, p-nitrobenzyl, p-halobenzyl, 2,6- Dichlorobenzyl, p-cyanobenzyl, p-phenylbenzyl, 2-picoryl, 4-picoryl, 3-methyl-2-picoryl N-oxide, diphenylmethyl, p, p'-dinitrobenzhydryl, 5-dibenzosveryl , Triphenylmethyl, α-naphthyldiphenylmethyl, p-methoxyphenyldiphenylmethyl, di (p-methoxyphenyl) phenylmethyl, tri (p-methoxyphenyl) methyl, 4- (4'-bromophenacillo) Xiphenyl) diphenylmethyl, 4,4', 4''-tris (4,5-dichlorophthalimidephenyl) methyl, 4,4', 4''-tris (levlinoyloxyphenyl) methyl, 4,4', 4''-Tris (benzoyloxyphenyl) methyl, 3- (imidazole-1-yl) bis (4', 4''-dimethoxyphenyl) methyl, 1,1-bis (4-methoxyphenyl) -1'- Pyrenylmethyl, 9-anthryl, 9- (9-phenyl) xanthenyl, 9- (9-phenyl-10-oxo) anthryl, 1,3-benzodithiolan-2-yl, benzoisothiazolyl S, S-dioxide, trimethylsilyl (TMS), triethylsilyl (TES), triisopropylsilyl (TIPS), dimethylisopropylsilyl (IPDMS), diethylisopropylsilyl (DEIPS), dimethylhexylsilyl, t-butyldimethylsilyl (TBDMS), t-butyldiphenylsilyl (TMS), triethylsilyl (TES), triisopropylsilyl (TIPS), dimethylisopropylsilyl (IPDMS), diethylisopropylsilyl (DEIPS), dimethylhexylsilyl, t-butyldimethylsilyl (TBDMS), t-butyldiphenylsilyl TBDPS), tribenzylsilyl, tri-p-kisilylsilyl, triphenylsilyl, diphenylmethylsilyl (DPMS), t-butylmethoxyphenylsilyl (TBMPS), formate, benzoylformate, acetate, chloroacetate, dichloroacetate, trichloroacetate , Trifluoroacetate, methoxyacetate, triphenylmethoxyacetate, phenoxyacetate, p-chlorophenoxyacetate, 3-phenylpropionate, 4-oxopentanoate (levulinate), 4,4- (ethylenedithio) pentanoate (revry) Noyldithioacetal), pivaloate, adamantoate, crotonate, 4-methoxycrotonate, benzoate, p-phenylbenzoate, 2,4,6-trimethylbenzoate (mesitoate), methylcarbonate, 9-fluorenylmethylcarbonate ( Fmoc), ethylcarbonate, 2,2,2-trichloroethylcarbonate (Troc), 2- (trimethylsilyl) ethylcarbonate (TMSEC), 2- (phenylsulfonyl) ethylcarbonate (Psec), 2- (tri) Phenylphosphonio) Ethylcarbonate (Peoc), isobutylcarbonate, vinylcarbonate, allylcarbonate, t-butylcarbonate (BOC), p-nitrophenylcarbonate, benzylcarbonate, p-methoxyben Zylcarbonate, 3,4-dimethoxybenzylcarbonate, o-nitrobenzylcarbonate, p-nitrobenzylcarbonate, S-benzylthiocarbonate, 4-ethoxy-1-naphthylcarbonate, methyldithiocarbonate, 2 -Iodobenzoate, 4-azidobutyrate, 4-nitro-4-methylpentanoate, o- (dibromomethyl) benzoate, 2-formylbenzenesulfonate, 2- (methylthiomethoxy) ethyl, 4- (methylthiomethoxy) butyrate , 2- (Methylthiomethoxymethyl) benzoate, 2,6-dichloro-4-methylphenoxyacetate, 2,6-dichloro-4- (1,1,3,3-tetramethylbutyl) phenoxyacetate, 2,4- Bis (1,1-dimethylpropyl) phenoxyacetate, chlorodiphenylacetate, isobutyrate, monosuccinoate, (E) -2-methyl-2-butenoate, o- (methoxyacyl) benzoate, α-naphthoate, nitrate, Alkyl N, N, N', N'-Tetramethylphosphologiamidate, Alkyl N-Phenylcarbamate, Borate, Dimethylphosphinochi oil, Alkyl 2,4-dinitrophenyl sulfide, Sulfate, Methane sulfonate (mesylate) , Benzene sulfonate, and tosylate (Ts).

In some embodiments, the substituent present on the sulfur atom is a sulfur protecting group (also referred to as a "thiol protecting group"). Sulfur protective groups include, but are not limited to -R ^aa , -N (R ^bb ) ₂ , -C (= O) SR ^aa , -C (= O) R ^aa , -CO ₂ R ^aa , -C (= O). ) N (R ^bb ) ₂ , -C (= NR ^bb ) R ^aa , -C (= NR ^bb ) OR ^aa , -C (= NR ^bb ) N (R ^bb ) ₂ , -S (= O) R ^aa , -SO ₂ R ^aa , -Si (R ^aa ) ₃ , -P (R ^cc ) ₂ , -P (R ^cc ) ₃ , -P (= O) ₂ R ^aa , -P (= O) (R ^aa) ) ₂ , -P (= O) (OR ^cc ) ₂ , -P (= O) ₂ N (R ^bb ) ₂ and -P (= O) (NR ^bb ) ₂ , where R ^aa , R ^bb and ^Rcc are as described herein. Sulfur protecting groups are well known in the art and are described in detail in the Protecting Groups in Organic Synthesis (TW Greene and PGM Wuts, 3rd Edition, John Wiley & Sons, 1999), which is incorporated herein by reference. Including things.

である。 As used herein, "leaving group" or "LG" is a term understood herein to refer to a molecular fragment that disengages with a pair of electrons upon anisotropic bond cleavage. The molecular fragment is an anion or a neutral molecule. See, for example, Smith, March Advanced Organic Chemistry, 6th Edition (501-502). Examples of suitable leaving groups include, but are not limited to, halides (chlorides, bromides or iodides), alkoxycarbonyloxy, aryloxycarbonyloxy, alkanesulfonyloxy, allenesulfonyloxy, alkyl-carbonyloxy (eg acetoxy). , Arylcarbonyloxy, aryloxy, methoxy, N, O-dimethylhydroxylamino, pixyl, halides, -NO ₂ , trialkylammonium and aryliodonium salts. In some embodiments, the leaving group is a sulfonic acid ester. In some embodiments, the sulfonic acid ester comprises the formula -OSO ₂ R ^LG1 , where the R ^LG1 is alkyl (optionally), alkenyl (optionally substituted), heteroalkyl (optionally substituted). , Aryl (optionally substituted), Heteroaryl (optionally substituted), Arylalkyl (optionally substituted), and Heteroarylalkyl (optionally substituted). Will be done. In some ^{embodiments, R LG1} is a substituted or unsubstituted _C 1 -C ₆ alkyl. In some embodiments, ^RLG1 is methyl. In some embodiments, the R ^{LG 1} is -CF ₃ . In some embodiments, ^RLG1 is a substituted or unsubstituted aryl. In some embodiments, ^RLG1 is a substituted or unsubstituted phenyl. In some embodiments, the ^RLG1 is

Is.

In some cases, the leaving group is toluene sulfonate (tosylate, Ts), methane sulfonate (mesylate, Ms), p-bromobenzenesulfonyl (brosylate, Bs), or trifluoromethanesulfonate (triflate, Tf). ). In some cases, the leaving group is brosilate (p-bromobenzenesulfonyl). In some cases, the leaving group is nosylate (2-nitrobenzenesulfonyl). In some embodiments, the leaving group is a sulfonate-containing group. In some embodiments, the leaving group is a tosylate group. The leaving group may also be a phosphine oxide (eg, one formed during the Mitsunobu reaction) or an internal leaving group such as an epoxide or cyclic sulfate ester.

These and other exemplary substituents are described in more detail in the detailed description, drawings, examples and claims. The present invention is not intended to be limited in any way by the above exemplary substituent listing.

Other Definitions The following definitions are more general terms used throughout this application.

As used herein, the term "pharmaceutically acceptable salt" is suitable for use in contact with human and lower animal tissues, to the extent of valid medical judgment. Salt that is not excessively toxic, irritating, allergic, etc., and is balanced by a reasonable effect / risk ratio. Pharmaceutically acceptable salts are well known in the art. For example, Berger et al. Describe in detail pharmaceutically acceptable salts in J. Pharmaceutical Sciences, 1977, 66, 1-19, which is incorporated herein by reference. Pharmaceutically acceptable salts of the compounds of the invention include those derived from suitable inorganic and organic acids and bases. Examples of pharmaceutically acceptable non-toxic acid addition salts are by inorganic acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid and perchloric acid, or by acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid. , Amino group salts formed with an organic acid such as succinic acid or malonic acid, or using other methods known in the art such as ion exchange. Other pharmaceutically acceptable salts include adipate, alginate, ascorbate, asparagate, benzenesulfonate, benzoate, bicarbonate, borate, butyrate, cypress acid, Camper sulfonate, citrate, cyclopentanepropionate, digluconate, dodecyl sulfate, ethane sulfonate, nitate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulfate Salts, heptaneates, hexanenates, hydrogen iodates, 2-hydroxy-ethane sulfonates, lactobionates, lactates, laurates, lauryl sulfates, malate, maleates, malonates , Methansulfonate, 2-naphthalene sulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, Phosphate, picphosphate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, valerate, etc. Can be mentioned. Salts derived from suitable bases include alkali metal salts, alkaline earth metal salts, ammonium salts and N ⁺ (C _1-4 alkyl) ₄ ^- salts. Typical alkaline and alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium and the like. Additional pharmaceutically acceptable salts are, where appropriate, non-toxic ammonium, quaternary ammonium, as well as halides, hydroxides, carboxylates, sulfates, phosphates, nitrates, lower alkylsulfons Contains amine cations formed with counter ions such as acid salts and aryl sulfonates.

The term "solvate" refers to the form of a compound or salt thereof, which is usually associated with a solvent by a solvolytic reaction. This physical association may include hydrogen bonds. Examples of ordinary solvents include water, methanol, ethanol, acetic acid, DMSO, THF, diethyl ether and the like. The compounds of the present invention may be prepared, for example, in crystalline form or may be solvated. Suitable solvates include pharmaceutically acceptable solvates and further include both stoichiometric and non-stoichiometric solvates. In some examples, the solvate could be isolated if, for example, one or more solvent molecules are incorporated into the crystalline lattice of the crystalline solid. "Solvate" includes both solution phase and separable solvate. Typical solvates include hydrates, etanolates and metanolates.

The term "hydrate" refers to a compound that is associated with water. Typically, the number of water molecules contained in the hydrate of a compound is in a predetermined ratio to the number of compound molecules in the hydrate. Therefore, the hydrate of a compound can be represented, for example, by the general formula R · xH ₂ O, where R is the compound, where x is a number greater than 0. A given compound can form more than one type of hydrate, eg monohydrate (x is 1), lower hydrate (x is greater than 0 and less than 1). Numbers, such as hemihydrate (R. 0.5H ₂ O)), and polyhydrates (x is a number greater than 0, such as dihydrate (R. 2H ₂ O) and hexahydrate. Japanese product (R ・ 6H ₂ O)) is included.

The term "tautomer" refers to a compound that is an exchangeable form of the structure of a particular compound, which differs in transpose of hydrogen atoms and electrons. Therefore, the two structures can be in equilibrium through the motion of π electrons and atoms (usually H). For example, enols and ketones are tautomers. This is because they are rapidly interconverted by treatment with either acids or bases. Another example of a tautomer is the acid and nitro form of phenylnitromethane, which is also formed by treatment with acid or base. The tautomeric form may be suitable for achieving optimal chemical reactivity and biological activity of the compound of interest.

It should also be understood that compounds having the same molecular formula but different bonding properties or arrangements of their atoms or arrangement of their atoms in space are called "isomers". Isomers with different arrangements of these atoms in space are called "stereoisomers".

The stereoisomers, which are mirror images of one other stereoisomer, are called "diastereomers", and the mirror images of each other, which cannot be superimposed, are called "enantiomers". A pair of enantiomers is conceivable if the compound has an asymmetric center, for example if it is attached to four different groups. Enantiomers can be characterized by the absolute configuration of their asymmetric centers and are described by the R- and S-arrangement rules of Cahn and Prelog, or by the mode in which the molecule rotates in a plane of polarization. , Designated as right-handed or left-handed (ie, as (+) or (-)-isomers, respectively). Chiral compounds can exist as individual enantiomers or as a mixture thereof. Mixtures containing equal proportions of enantiomers are referred to as "racemic mixtures".

The term "polymorph" refers to the crystalline form of a compound (or a salt, hydrate or solvate thereof). All polymorphs have the same elemental composition. Different crystal morphologies usually have different X-ray diffraction patterns, infrared spectra, melting points, densities, hardness, crystal shapes, optical and electronic properties, stability and solubility. Depending on the recrystallization solvent, the rate of crystallization, the storage temperature, and other factors, one crystal morphology may predominate. Various polymorphisms of compounds can be prepared by crystallization under different conditions.

The term "prodrug" refers to a compound that has a cleavable group and is a compound of the invention by solvolysis or under physiological conditions, which is pharmaceutically active in vivo. Examples thereof include, but are not limited to, N-alkylmorpholine esters such as choline ester derivatives. Other derivatives of the compounds of the invention are active in both their acid and acid derivatives forms, but often offer the benefits of solubility, histocompatibility or delayed release in mammals in acid sensitive forms (in acid sensitive forms). See Bundgard, H., Design of Prodrugs, pp. 7-9, 21-24, Elsevier, Amsterdam 1985). Prodrugs are acid derivatives well known to those skilled in the art, such as esters prepared by the reaction of a mic acid with a suitable alcohol, or amides prepared by the reaction of a phobic acid compound with a substituted or unsubstituted amine, or acid anhydride. Includes compounds or mixed anhydrides. Simple aliphatic or aromatic esters, amides and anhydrides derived from pendant acidic groups on the compounds of the invention are special prodrugs. In some cases, it is desirable to prepare a double ester type prodrug such as (acyloxy) alkyl ester or ((alkoxycarbonyl) oxy) alkyl ester. In particular, the compounds of the present invention _C 1 -C _{8 alkyl,} C 2 -C _{8 alkenyl,} C 2 -C ₈ (e.g. formula (A), (I-11 ), (II), or compounds of (V)) Alkinyl, aryl, C _7- C _12- substituted aryl, and C _7- C ₁₂ aryl alkyl esters.

FIG. 1 shows an isobologram demonstrating a synergistic effect between compound (A-17) and a BTK inhibitor. The points below the 1-1 line connecting the X and Y axes are "synergistic", the points near the line are "additive", and the points above are antagonistic.

Detailed Description of the Invention In vitro screening for several kinases (eg BTK, HCK, TAK1, HPK1) as part of an effort to identify novel treatments for Waldenstrem macrogamma globulinemia. Was done. These kinases are involved in the regulation of abnormal cell proliferation associated with this condition. In addition, cell-based screening was performed on model strains of several disease states of Waldenström macrogamma globulinemia (eg BCWM.1, MWCL-1). Based on these screening efforts and subsequent read optimization, any one compound of formula (A), (I-11), (II) and (V) (eg, formula (A-1)- (A-18) compound) was identified.

の化合物、ならびにその医薬的に許容可能な塩、溶媒和物、水和物、多形、共結晶、互変異性体、立体異性体、同位体標識された誘導体およびプロドラッグを提供し；
式中：
Ｒ^Ａの各々の場合は、独立して、水素、ハロゲン、任意置換のアルキル、任意置換のカルボシクリル、−ＯＲ^Ａ１、−Ｎ（Ｒ^Ａ１）_２、−ＣＮ、−Ｃ（＝Ｏ）Ｒ^Ａ１、−Ｃ（＝Ｏ）ＯＲ^Ａ１、−Ｃ（＝Ｏ）Ｎ（Ｒ^Ａ１）_２、−ＮＯ_２、−ＮＲ^Ａ１Ｃ（＝Ｏ）Ｒ^Ａ１、−ＮＲ^Ａ１Ｃ（＝Ｏ）ＯＲ^Ａ１、−ＮＲ^Ａ１Ｓ（＝Ｏ）_２Ｒ^Ａ１、−Ｓ（＝Ｏ）_２Ｒ^Ａ１または−Ｓ（＝Ｏ）_２Ｎ（Ｒ^Ａ１）_２からなる群より選択され；
Ｒ^Ｂの各々の場合は、独立して、水素、ハロゲン、任意置換のアルキル、任意置換のカルボシクリル、任意置換のヘテロシクリル、任意置換のアリール、任意置換のヘテロアリール、−ＯＲ^Ａ１、−Ｎ（Ｒ^Ａ１）_２、−ＣＮ、−Ｃ（＝Ｏ）Ｒ^Ａ１、−Ｃ（＝Ｏ）ＯＲ^Ａ１、−Ｃ（＝Ｏ）Ｎ（Ｒ^Ａ１）_２、−ＮＯ_２、−ＮＲ^Ａ１Ｃ（＝Ｏ）Ｒ^Ａ１、−ＮＲ^Ａ１Ｃ（＝Ｏ）ＯＲ^Ａ１、−ＮＲ^Ａ１Ｓ（＝Ｏ）_２Ｒ^Ａ１、−Ｓ（＝Ｏ）_２Ｒ^Ａ１または−Ｓ（＝Ｏ）_２Ｎ（Ｒ^Ａ１）_２からなる群より選択され；
Ｒ^Ａ１の各々の場合は、独立して、水素、任意置換のアシル、任意置換のアルキル、任意置換のアルケニル、任意置換のアルキニル、任意置換のカルボシクリル、任意置換のヘテロシクリル、任意置換のアリール、任意置換のヘテロアリール、窒素原子に結合している場合は窒素保護基、酸素原子に結合している場合は酸素保護基、および硫黄原子に結合している場合は硫黄保護基からなる群より選択されるか、または２個のＲ^Ａ１基が、連結されて、任意に置換されたヘテロ環式環を形成し；
環Ｂ中に含まれる１つのＡは、ＣＲ^Ｙであり；
環Ｂ中に含まれるもう１つのＡは、ＣＲ^ＹまたはＮであり；
Ｒ^Ｙの各々の場合は、独立してＨ、ハロゲンまたは置換もしくは未置換のＣ_１−６のアルキル基であり；
Ｒ^Ｘの各々の場合は、任意置換のカルボシクリル、任意置換のヘテロシクリル、任意置換のアリール、任意置換のヘテロアリール、および−Ｎ（Ｒ^Ａ１）（Ｒ^Ｘａ）からなる群より独立して選択され；
Ｒ^Ｘａの各々の場合は、水素、任意置換のアルキル、任意置換のアルケニル、任意置換のアルキニル、任意置換のカルボシクリル、任意置換のヘテロシクリル、任意置換のアリール、任意置換のヘテロアリール、−Ｃ（＝Ｏ）Ｒ^Ａ１、−Ｃ（＝Ｏ）ＯＲ^Ａ１、−Ｃ（＝Ｏ）Ｎ（Ｒ^Ａ１）_２、−Ｓ（＝Ｏ）Ｒ^Ａ１、−Ｓ（＝Ｏ）Ｎ（Ｒ^Ａ１）_２、−Ｓ（＝Ｏ）_２Ｒ^Ａ１、−Ｓ（＝Ｏ）_２ＯＲ^Ａ１、−Ｓ（＝Ｏ）_２Ｎ（Ｒ^Ａ１）_２、−Ｎ（Ｒ^Ａ１）_２および窒素保護基からなる群より選択され；
ｋは、０、１、２、３または４であり；
ｌは、１、２、３、４または５であり；
ＱとＵとは、一緒にされて、−ＮＲ^Ａ（Ｃ＝Ｏ）−または−（Ｃ＝Ｏ）ＮＲ^Ａ−となり；ならびに
Ｒ^Ｄは、本明細書において記載されるとおりの求電子部分である。 In one aspect, the present invention describes the formula (A):

Compounds, as well as pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, character isomers, isotope-labeled derivatives and prodrugs thereof;
During the ceremony:
In ^{each case of RA} , independently, hydrogen, halogen, optionally substituted alkyl, optionally substituted carbocyclyl, -OR ^A1 , -N ( ^RA1 ) ₂ , -CN, -C (= O) ^RA1 , -C (= O) OR ^A1 , -C (= O) N ( ^RA1 ) ₂ , -NO ₂ , -NR ^A1 C (= O) R ^A1 , -NR ^A1 C (= O) OR ^A1 , -NR Selected from the group consisting of ^A1 S (= O) ₂ R ^A1 , -S (= O) ₂ R ^A1 or -S (= O) ₂ N ( ^RA1 ) _2;
For each R ^B, is independently hydrogen, halogen, optionally substituted alkyl, the optionally substituted carbocyclyl, any substituted heterocyclyl, any substituted aryl, optionally substituted heteroaryl, -OR A1, ^{-N (R A1} ) ₂ , -CN, -C (= O) ^RA1 , -C (= O) OR ^A1 , -C (= O) N ( ^RA1 ) ₂ , -NO ₂ , -NR ^A1 C (= O) ^RA1 , -NR ^A1 C (= O) OR ^A1 , -NR ^A1 S (= O) ₂ ^RA1 , -S (= O) ₂ ^RA1 or -S (= O) ₂ N ( ^RA1 ) ₂ Selected from the group;
For each R ^A1, independently, hydrogen, optional substituted acyl, the optionally substituted alkyl, the optionally substituted alkenyl, arbitrary substituted alkynyl, any substitution carbocyclyl, any substituted heterocyclyl, any substituted aryl, optionally Selected from the group consisting of a substituted heteroaryl, a nitrogen protecting group when bonded to a nitrogen atom, an oxygen protecting group when bonded to an oxygen atom, and a sulfur protecting group when bonded to a sulfur atom. Or two ^RA1 groups are linked to form an arbitrarily substituted heterocyclic ring;
One A contained in the ring B is a CR ^Y;
Another A contained in the ring B is a CR ^Y or N;
^{Each case of RY} is an independently H, halogen or substituted or unsubstituted C _1-6 alkyl group;
For each of R ^X, optionally substituted carbocyclyl, is independently selected from the group consisting of optionally substituted heterocyclyl, any substituted aryl, optionally substituted heteroaryl, and ^{-N (R A1) (R Xa} );
In ^{each case of RXa} , hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, -C (= O) ^RA1 , -C (= O) OR ^A1 , -C (= O) N ( ^RA1 ) ₂ , -S (= O) ^RA1 , -S (= O) N ( ^RA1 ) ₂ ,- Selected from the group consisting of S (= O) ₂ ^RA1 , -S (= O) ₂ OR ^A1 , -S (= O) ₂ N ( ^RA1 ) ₂ , -N ( ^RA1 ) _{2 and nitrogen-protecting groups.} ;
k is 0, 1, 2, 3 or 4;
l is 1, 2, 3, 4 or 5;
Q and U are combined to form -NR ^A (C = O)-or-(C = O) NR ^A- ; and ^RD is the electrophilic portion as described herein. is there.

からなる群からの化合物、およびその医薬的に許容可能な塩を提供する。 In some embodiments, the present invention

Provided are compounds from the group consisting of, and pharmaceutically acceptable salts thereof.

In another aspect, the invention provides a method for treating Waldenstrem macrogamma globulinemia (WM) in a subject using the compounds of the invention. The method comprises administering to a subject in need thereof an effective amount of a compound of the invention. Also provided are the compounds of the invention on Breton-type tyrosine kinase (BTK), interleukin-1 receptor-related kinase 1 (IRAK1), interleukin-1 receptor-related kinase 4 (IRAK4), on the X chromosome. In combination with inhibitors of bone marrow on X chromosome kinase (BMX), phosphoinositide 3-kinase (PI3K), transforming growth factor b-activated kinase-1 (TAK1), and / or Src family kinase, A method of treating other B-cell neoplasms. In some embodiments, one or more compounds of the invention are used in combination with an inhibitor of phosphoinositide 3-kinase delta isoform (PI3Kδ). In some embodiments, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more combinations of the agents described herein are used to treat WM. In some embodiments, the agents described herein are Bruton's tyrosine kinase (BTK), interleukin-1 receptor-related kinase 1 (IRAK1), interleukin-1 receptor-related kinase 4 (IRAK4), X chromosome. Used in combination with kinase inhibitors such as upper bone marrow kinase (BMX) and / or phosphoinositide 3-kinase (PI3K), transforming growth factor b-activated kinase-1 (TAK1), and / or Src family kinase inhibitors. ..

Waldenström macrogamma globulinemia (WM) is a well-defined clinicopathological entity that results from the accumulation of clonally associated lymphatic plasma cells that secrete the monoclonal IgM protein, primarily in the bone marrow. This condition is considered to correspond to lymphoplasmacytic lymphoma (LPL) as defined by the World Health Organization classification system. Genetic factors play an important role in the pathogenesis of WM, with 25% of patients exhibiting a family history. IgM monoclonal macrogamma globulinemia (MGUS) of unknown significance often precedes the onset of WM.

As used herein, B cell neoplasms include both Hodgkin lymphoma and non-Hodgkin lymphoma. Classic Hodgkin lymphoma (HL) includes nodular sclerosing HL, mixed cell subtype, Lymphocyte-rich or Lymphocytic predominance and Lymphocyte depleted. Includes various subtypes. Examples of B-cell non-Hodgkin's lymphoma include, but are not limited to, Waldenstrem macrogamma globulinemia, diffuse large B-cell lymphoma, follicular lymphoma, mucosal-related lymphoid lymphoma (MALT), and small lymphocytic lymphoma. (Overlapping with chronic lymphocytic leukemia), mantle cell lymphoma (MCL), Berkitt lymphoma, medial large cell type B cell lymphoma, nodular marginal zone B cell lymphoma (NMZL), splenic marginal zone lymphoma (SMZL) , Intravascular large B-cell lymphoma, primary exudative lymphoma, and lymphoma-like granulomatosis.

の化合物、ならびにその医薬的に許容可能な塩、溶媒和物、水和物、多形、共結晶、互変異性体、立体異性体、同位体標識された誘導体およびプロドラッグを投与され；
式中：
Ｒ^Ａの各々の場合は、独立して、水素、ハロゲン、任意置換のアルキル、任意置換のカルボシクリル、−ＯＲ^Ａ１、−Ｎ（Ｒ^Ａ１）_２、−ＣＮ、−Ｃ（＝Ｏ）Ｒ^Ａ１、−Ｃ（＝Ｏ）ＯＲ^Ａ１、−Ｃ（＝Ｏ）Ｎ（Ｒ^Ａ１）_２、−ＮＯ_２、−ＮＲ^Ａ１Ｃ（＝Ｏ）Ｒ^Ａ１、−ＮＲ^Ａ１Ｃ（＝Ｏ）ＯＲ^Ａ１、−ＮＲ^Ａ１Ｓ（＝Ｏ）_２Ｒ^Ａ１、−Ｓ（＝Ｏ）_２Ｒ^Ａ１または−Ｓ（＝Ｏ）_２Ｎ（Ｒ^Ａ１）_２からなる群より選択され；
Ｒ^Ｂの各々の場合は、独立して、水素、ハロゲン、任意置換のアルキル、任意置換のカルボシクリル、任意置換のヘテロシクリル、任意置換のアリール、任意置換のヘテロアリール、−ＯＲ^Ａ１、−Ｎ（Ｒ^Ａ１）_２、−ＣＮ、−Ｃ（＝Ｏ）Ｒ^Ａ１、−Ｃ（＝Ｏ）ＯＲ^Ａ１、−Ｃ（＝Ｏ）Ｎ（Ｒ^Ａ１）_２、−ＮＯ_２、−ＮＲ^Ａ１Ｃ（＝Ｏ）Ｒ^Ａ１、−ＮＲ^Ａ１Ｃ（＝Ｏ）ＯＲ^Ａ１、−ＮＲ^Ａ１Ｓ（＝Ｏ）_２Ｒ^Ａ１、−Ｓ（＝Ｏ）_２Ｒ^Ａ１または−Ｓ（＝Ｏ）_２Ｎ（Ｒ^Ａ１）_２、からなる群より選択され；
Ｒ^Ａ１の各々の場合は、独立して、水素、任意置換のアシル、任意置換のアルキル、任意置換のアルケニル、任意置換のアルキニル、任意置換のカルボシクリル、任意置換のヘテロシクリル、任意置換のアリール、任意置換のヘテロアリール、窒素原子に結合している場合は窒素保護基、酸素原子に結合している場合は酸素保護基、および硫黄原子に結合している場合は硫黄保護基からなる群より選択されるか、または２個のＲ^Ａ１基は、連結されて、任意に置換されたヘテロ環式環を形成し；
Ｒ^Ｘの各々の場合は任意置換のカルボシクリル、任意置換のヘテロシクリル、任意置換のアリール、任意置換のヘテロアリール、および−Ｎ（Ｒ^Ａ１）（Ｒ^Ｘａ）からなる群より独立して選択され；
Ｒ^Ｘａの各々の場合は、水素、任意置換のアルキル、任意置換のアルケニル、任意置換のアルキニル、任意置換のカルボシクリル、任意置換のヘテロシクリル、任意置換のアリール、任意置換のヘテロアリール、−Ｃ（＝Ｏ）Ｒ^Ａ１、−Ｃ（＝Ｏ）ＯＲ^Ａ１、−Ｃ（＝Ｏ）Ｎ（Ｒ^Ａ１）_２、−Ｓ（＝Ｏ）Ｒ^Ａ１、−Ｓ（＝Ｏ）Ｎ（Ｒ^Ａ１）_２、−Ｓ（＝Ｏ）_２Ｒ^Ａ１、−Ｓ（＝Ｏ）_２ＯＲ^Ａ１、−Ｓ（＝Ｏ）_２Ｎ（Ｒ^Ａ１）_２、−Ｎ（Ｒ^Ａ１）_２および窒素保護基からなる群より選択され；
ｋは、０、１、２、３または４であり；
ｌは、１、２、３、４または５であり；
ＱとＵとは、一緒にされて、−ＮＲ^Ａ（Ｃ＝Ｏ）−または−（Ｃ＝Ｏ）ＮＲ^Ａ−となり；ならびに
Ｒ^Ｄは、本明細書において記載されるとおりの求電子部分である。 In some embodiments, the subject is of formula (A) :.

Compounds, as well as pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, character isomers, isotope-labeled derivatives and prodrugs thereof;
During the ceremony:
In ^{each case of RA} , independently, hydrogen, halogen, optionally substituted alkyl, optionally substituted carbocyclyl, -OR ^A1 , -N ( ^RA1 ) ₂ , -CN, -C (= O) ^RA1 , -C (= O) OR ^A1 , -C (= O) N ( ^RA1 ) ₂ , -NO ₂ , -NR ^A1 C (= O) R ^A1 , -NR ^A1 C (= O) OR ^A1 , -NR Selected from the group consisting of ^A1 S (= O) ₂ R ^A1 , -S (= O) ₂ R ^A1 or -S (= O) ₂ N ( ^RA1 ) _2;
For each R ^B, is independently hydrogen, halogen, optionally substituted alkyl, the optionally substituted carbocyclyl, any substituted heterocyclyl, any substituted aryl, optionally substituted heteroaryl, -OR A1, ^{-N (R A1} ) ₂ , -CN, -C (= O) ^RA1 , -C (= O) OR ^A1 , -C (= O) N ( ^RA1 ) ₂ , -NO ₂ , -NR ^A1 C (= O) ^RA1 , -NR ^A1 C (= O) OR ^A1 , -NR ^A1 S (= O) ₂ ^RA1 , -S (= O) ₂ ^RA1 or -S (= O) ₂ N ( ^RA1 ) _2, Selected from the group consisting of;
For each R ^A1, independently, hydrogen, optional substituted acyl, the optionally substituted alkyl, the optionally substituted alkenyl, arbitrary substituted alkynyl, any substitution carbocyclyl, any substituted heterocyclyl, any substituted aryl, optionally Selected from the group consisting of a substituted heteroaryl, a nitrogen protecting group when bonded to a nitrogen atom, an oxygen protecting group when bonded to an oxygen atom, and a sulfur protecting group when bonded to a sulfur atom. Or two ^RA1 groups are linked to form an arbitrarily substituted heterocyclic ring;
Carbocyclyl optionally substituted in the case of each of R ^X, any substituted heterocyclyl, any substituted aryl, optionally substituted heteroaryl, and -N (R A1) independently from the group consisting of ^{(R Xa)} is selected;
In ^{each case of RXa} , hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, -C (= O) ^RA1 , -C (= O) OR ^A1 , -C (= O) N ( ^RA1 ) ₂ , -S (= O) ^RA1 , -S (= O) N ( ^RA1 ) ₂ ,- Selected from the group consisting of S (= O) ₂ ^RA1 , -S (= O) ₂ OR ^A1 , -S (= O) ₂ N ( ^RA1 ) ₂ , -N ( ^RA1 ) _{2 and nitrogen-protecting groups.} ;
k is 0, 1, 2, 3 or 4;
l is 1, 2, 3, 4 or 5;
Q and U are combined to form -NR ^A (C = O)-or-(C = O) NR ^A- ; and ^RD is the electrophilic portion as described herein. is there.

またはその医薬的に許容可能な塩を投与される。 In some embodiments, the subject is compound (A-1) :.

Or the pharmaceutically acceptable salt thereof is administered.

またはその医薬的に許容可能な塩を投与される。 In some embodiments, the subject is compound (A-2) :.

Or the pharmaceutically acceptable salt thereof is administered.

またはその医薬的に許容可能な塩を投与される。 In some embodiments, the subject is compound (A-3) :.

Or the pharmaceutically acceptable salt thereof is administered.

またはその医薬的に許容可能な塩を投与される。 In some embodiments, the subject is compound (A-4):

Or the pharmaceutically acceptable salt thereof is administered.

またはその医薬的に許容可能な塩を投与される。 In some embodiments, the subject is compound (A-5) :.

Or the pharmaceutically acceptable salt thereof is administered.

またはその医薬的に許容可能な塩を投与される。 In some embodiments, the subject is compound (A-6) :.

Or the pharmaceutically acceptable salt thereof is administered.

またはその医薬的に許容可能な塩を投与される。 In some embodiments, the subject is compound (A-7) :.

Or the pharmaceutically acceptable salt thereof is administered.

またはその医薬的に許容可能な塩を投与される。 In some embodiments, the subject is compound (A-8) :.

Or the pharmaceutically acceptable salt thereof is administered.

またはその医薬的に許容可能な塩を投与される。 In some embodiments, the subject is compound (A-9) :.

Or the pharmaceutically acceptable salt thereof is administered.

またはその医薬的に許容可能な塩を投与される。 In some embodiments, the subject is compound (A-10) :.

Or the pharmaceutically acceptable salt thereof is administered.

またはその医薬的に許容可能な塩を投与される。 In some embodiments, the subject is compound (A-11) :.

Or the pharmaceutically acceptable salt thereof is administered.

またはその医薬的に許容可能な塩を投与される。 In some embodiments, the subject is compound (A-12) :.

Or the pharmaceutically acceptable salt thereof is administered.

またはその医薬的に許容可能な塩を投与される。 In some embodiments, the subject is compound (A-13) :.

Or the pharmaceutically acceptable salt thereof is administered.

またはその医薬的に許容可能な塩を投与される。 In some embodiments, the subject is compound (A-14) :.

Or the pharmaceutically acceptable salt thereof is administered.

またはその医薬的に許容可能な塩を投与される。 In some embodiments, the subject is compound (A-15) :.

Or the pharmaceutically acceptable salt thereof is administered.

またはその医薬的に許容可能な塩を投与される。 In some embodiments, the subject is compound (A-16) :.

Or the pharmaceutically acceptable salt thereof is administered.

またはその医薬的に許容可能な塩を投与される。 In some embodiments, the subject is compound (A-17) :.

Or the pharmaceutically acceptable salt thereof is administered.

またはその医薬的に許容可能な塩を投与される。 In some embodiments, the subject is compound (A-18) :.

Or the pharmaceutically acceptable salt thereof is administered.

のものである。ある態様において、環Ａは、式：

のものである。ある態様において、環Ａは、式：

のものである。ある態様において、環Ａは、式：

のものである。ある態様において、環Ａは、式：

のものである。ある態様において、ｋは、２である。ある態様において、環Ａは、式：

のものである。ある態様において、環Ａは、式：

のものである。ある態様において、環Ａは、式：

のものである。ある態様において、環Ａは、式：

のものである。ある態様において、環Ａは、式：

のものである。ある態様において、環Ａは、式：

のものである。ある態様において、ｋは、３である。ある態様において、環Ａは、式：

のものである。ある態様において、環Ａは、式：

のものである。ある態様において、環Ａは、式：

のものである。ある態様において、ｋは、４である。ある態様において、環Ａは、式：

のものである。 The compound of formula (A) comprises a phenyl ring A optionally substituted with ^{one or more RA groups.} In some embodiments, k is 0. In some embodiments, the ring A is of formula:

belongs to. In some embodiments, the ring A is of formula:

belongs to. In some embodiments, the ring A is of formula:

belongs to. In some embodiments, the ring A is of formula:

belongs to. In some embodiments, the ring A is of formula:

belongs to. In some embodiments, k is 2. In some embodiments, the ring A is of formula:

belongs to. In some embodiments, the ring A is of formula:

belongs to. In some embodiments, the ring A is of formula:

belongs to. In some embodiments, the ring A is of formula:

belongs to. In some embodiments, the ring A is of formula:

belongs to. In some embodiments, the ring A is of formula:

belongs to. In some embodiments, k is 3. In some embodiments, the ring A is of formula:

belongs to. In some embodiments, the ring A is of formula:

belongs to. In some embodiments, the ring A is of formula:

belongs to. In some embodiments, k is 4. In some embodiments, the ring A is of formula:

belongs to.

In the compound of formula (A), ring A may be substituted with ^{one or more RA groups.} In some embodiments, at least one ^RA is H. In some embodiments, the at least two ^RA groups are H. In some embodiments, at least three ^RA groups are H. In some embodiments, at least four ^RA groups are H. In some embodiments, at least one ^RA is not H. In some embodiments, at least two ^RA groups are not H. In some embodiments, at least three ^RA groups are not H. In some embodiments, at least one ^RA is a halogen. In some embodiments, at least one ^RA is F. In some embodiments, at least one ^RA is Cl. In some embodiments, at least one ^RA is Br. In some embodiments, at least one ^RA is I (iodine). In some embodiments, one ^RA is F. In some embodiments, one ^RA is Cl. In some embodiments, at least one ^RA is a substituted alkyl. In some embodiments, at least one ^RA is an unsubstituted alkyl. In some embodiments, at least one ^RA is a substituted C _1-6 alkyl. In some embodiments, at least one ^RA is an unsubstituted C _1-6 alkyl. In some embodiments, at least one ^RA is methyl. In some embodiments, at least one ^RA is ethyl. In some embodiments, at least one ^RA is propyl. In some embodiments, at least one ^RA is butyl. In some embodiments, at least one ^RA is a substituted carbocyclyl. In some embodiments, at least one ^RA is an unsubstituted carbocyclyl. In some embodiments, at least one ^RA is -OR ^A1 . In some embodiments, at least one ^RA is —O (C _1-6 alkyl), where the alkyl is substituted or unsubstituted. In some embodiments, at least one ^RA is -OMe. In some embodiments, at least one ^RA is -OH. In some embodiments, at least one ^RA is -N ( ^RA1 ) ₂ . In some embodiments, at least one ^RA is -NH ₂ . In some embodiments, at least one ^RA is -CN. In some embodiments, at least one ^RA is -C (= O) ^RA1 . In some embodiments, at least one ^RA is acetyl. In some embodiments, at least one ^RA is -C (= O) OR ^A1 . In some embodiments, at least one ^RA is -C (= O) N ( ^RA1 ) ₂ . In some embodiments, at least one ^RA is -C (= O) NHR ^A1 . In some embodiments, at least one ^RA is -C (= O) NH (C _1-6 alkyl), where the alkyl is substituted or unsubstituted. In some embodiments, at least one ^RA is -C (= O) NHMe. In some embodiments, at least one ^RA is -C (= O) NH ₂ . In some embodiments, at least one ^RA is -NO ₂ . In some embodiments, at least one ^RA is -NR ^A1 C (= O) ^RA1 . In some embodiments, at least one ^RA is -NR ^A1 C (= O) OR ^A1 . In some embodiments, at least one ^RA is -NR ^A1 S (= O) ₂ ^RA1 . In some embodiments, at least one ^{R A,} is ^{_{-NHS (= O) 2 R A1}} . In some embodiments, at least one ^RA is -NHS (= O) ₂ (C _1-6 alkyl), where the alkyl is substituted or unsubstituted. In some embodiments, at least one ^RA is -NHS (= O) ₂ Me. In some embodiments, at least one ^RA is -S (= O) ₂ ^RA1 . In some embodiments, at least one ^RA is -S (= O) ₂ N ( ^RA1 ) ₂ . In some embodiments, at least one ^RA is -S (= O) ₂ N ( ^RA1 ) ₂ . In some embodiments, at least one ^RA is -S (= O) ₂ N (C _1-6 alkyl) ₂ . In some embodiments, at least one ^RA is -S (= O) ₂ NH (C _1-6 alkyl). In some embodiments, at least one ^RA is -S (= O) ₂ NH (t-Bu). In some embodiments, at least one ^RA is -S (= O) ₂ NH ₂ .

In some embodiments, ^RA is -OR ^A1 ; k is 1. In some embodiments, ^RA is -O (C _1-6 alkyl); k is 1. In some embodiments, ^RA is -OMe; k is 1. In some embodiments, ^RA is -OH; k is 1.

In some embodiments, ^RA is a substituted C _1-6 alkyl; k is 1. In some embodiments, ^RA is an unsubstituted C _1-6 alkyl; k is 1. In some embodiments, ^RA is methyl; k is 1. In some embodiments, ^RA is -CF ₃ ; k is 1. In some embodiments, ^RA is ethyl; k is 1. In some embodiments, ^RA is propyl; k is 1. In some embodiments, ^RA is butyl; k is 1. In some embodiments, ^RA is propyl; k is 1. In some embodiments, ^RA is butyl; k is 1.

In some embodiments, ^RA is a halogen; k is 1. In some embodiments, ^RA is F; k is 1. In some embodiments, ^RA is Cl; k is 1. In some embodiments, ^RA is Br; k is 1. In some embodiments, ^RA is I (iodine); k is 1.

In some embodiments, ^{one case of RA} is a halogen; ^{another case of RA} is a substituted C _1-6 alkyl; k is 2. In some embodiments, one case of ^{RA is F; another case of RA} is a substituted C _1-6 alkyl; k is 2. In some embodiments, one case of ^{RA is Cl; another case of RA} is a substituted C _1-6 alkyl; k is 2. In some embodiments, ^{one case of RA} is a halogen; ^{another case of RA} is an unsubstituted C _1-6 alkyl; k is 2. In some embodiments, one case of ^{RA is F; another case of RA} is an unsubstituted C _1-6 alkyl; k is 2. In some embodiments, one case of ^{RA is Cl; another case of RA} is an unsubstituted C _1-6 alkyl; k is 2. In some embodiments, one case of ^{RA is halogen; another case of RA} is methyl; k is 2. In some embodiments, one case of ^{RA is F; another case of RA} is methyl; k is 2. In some embodiments, one case of ^{RA is Cl; another case of RA} is methyl; k is 2. In some embodiments, one case of ^RA is halogen; another case of ^RA _{is -CF 3} , and k is 2. In some embodiments, one case of ^RA is F; another case of ^RA _{is -CF 3} , and k is 2. In some embodiments, one case of ^RA is Cl; another case of ^RA _{is -CF 3} , and k is 2.

In some embodiments, at least one ^RA1 is H. In some embodiments, at least one ^RA1 is a substituted acyl. In some embodiments, at least one ^RA1 is an unsubstituted acyl. In some embodiments, at least one ^RA1 is acetyl. In some embodiments, at least one ^RA1 is a substituted alkyl. In some embodiments, at least one ^RA1 is an unsubstituted alkyl. In some embodiments, at least one ^RA1 is C _1-6 alkyl. In some embodiments, at least one ^RA1 is methyl. In some embodiments, at least one ^RA1 is ethyl. In some embodiments, at least one ^RA1 is propyl. In some embodiments, at least one ^RA1 is butyl. In some embodiments, at least one ^RA1 is a substituted alkenyl. In some embodiments, at least one ^RA1 is an unsubstituted alkenyl. In some embodiments, at least one ^RA1 is a substituted alkynyl. In some embodiments, at least one ^RA1 is an unsubstituted alkynyl. In some embodiments, at least one ^{R A1,} substituted carbocyclyl. In certain embodiments, at least one of R ^A1 is unsubstituted carbocyclyl. In some embodiments, at least one ^RA1 is a substituted heterocyclyl. In some embodiments, at least one ^RA1 is an unsubstituted heterocyclyl. In some embodiments, at least one ^RA1 is a substituted aryl. In some embodiments, at least one ^RA1 is an unsubstituted aryl. In some embodiments, at least one ^RA1 is a substituted phenyl. In some embodiments, at least one ^RA1 is unsubstituted phenyl. In some embodiments, at least one ^RA1 is a substituted heteroaryl. In some embodiments, at least one ^RA1 is an unsubstituted heteroaryl. In some embodiments, at least one ^RA1 is a substituted pyridyl. In some embodiments, at least one ^RA1 is an unsubstituted pyridyl. In some embodiments, at least one R ^A1, when attached to the nitrogen atom is a nitrogen protecting group. In some embodiments, at least one ^{R A1,} when attached to a nitrogen atom, Bn, BOC, Cbz, Fmoc, trifluoroacetyl, triphenylmethyl or Ts. In some embodiments, ^RA1 is an oxygen protecting group when attached to an oxygen atom. In some ^{embodiments, R A1,} if attached to an oxygen atom, a silyl, TBDPS, TBDMS, TIPS, TES , TMS, MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl or benzoyl. In some embodiments, ^RA1 is a sulfur protecting group when attached to a sulfur atom. In some ^{embodiments, R A1,} if attached to the sulfur atom, acetamidomethyl, t-Bu, 3- nitro-2-pyridine sulfenyl, 2-pyridine - a sulfenyl or triphenylmethyl.

In the compound of formula (A), the two ^RA1 groups are linked and optionally substituted carbocyclic rings, optionally substituted heterocyclic rings, optionally substituted aryl, or optionally substituted heterocycles. An aryl ring may be formed. In some embodiments, the two ^RA1 groups are linked to form a carbocyclic ring. In some embodiments, the two ^RA1 groups are linked to form an unsubstituted carbocyclic ring. In some embodiments, the two ^RA1 groups are linked to form a substituted heterocyclic ring. In some embodiments, the two ^RA1 groups are linked to form an unsubstituted heterocyclic ring. In some embodiments, the two ^RA1 groups are linked to form a substituted aryl ring. In some embodiments, the two ^RA1 groups are linked to form an unsubstituted aryl ring. In some embodiments, the two ^RA1 groups are linked to form a substituted phenyl ring. In some embodiments, the two ^RA1 groups are linked to form an unsubstituted phenyl ring. In some embodiments, the two ^RA1 groups are linked to form a substituted heteroaryl ring. In some embodiments, the two ^RA1 groups are linked to form an unsubstituted heteroaryl ring.

のものである。ある態様において、環Ｃは、式：

のものである。ある態様において、環Ｃは、式：

のものである。ある態様において、ｌは、２である。ある態様において、環Ｃは、式：

のものである。ある態様において、ｌは、２である。ある態様において、環Ｃは、式：

のものである。ある態様において、環Ｃは、式：

のものである。ある態様において、環Ｃは、式：

のものである。ある態様において、環Ｃは、式：

のものである。ある態様において、環Ｃは、式：

のものである。ある態様において、ｌは、３である。ある態様において、環Ｃは、式：

のものである。ある態様において、環Ｃは、式：

のものである。ある態様において、環Ｃは、式：

のものである。ある態様において、環Ｃは、式：

のものである。ある態様において、ｌは、４である。ある態様において、環Ｃは、式：

のものである。ある態様において、環Ｃは、式：

のものである。ある態様において、環Ｃは、式：

のものである。ある態様において、ｌは５である。ある態様において、環Ｃは、式：

のものである。 Compounds of formula (A) contains a phenyl ring C optionally substituted with one or more R ^B groups. In some embodiments, l is 1. In some embodiments, the ring C is represented by the formula:

belongs to. In some embodiments, the ring C is represented by the formula:

belongs to. In some embodiments, the ring C is represented by the formula:

belongs to. In some embodiments, l is 2. In some embodiments, the ring C is represented by the formula:

belongs to. In some embodiments, l is 2. In some embodiments, the ring C is represented by the formula:

belongs to. In some embodiments, the ring C is represented by the formula:

belongs to. In some embodiments, the ring C is represented by the formula:

belongs to. In some embodiments, the ring C is represented by the formula:

belongs to. In some embodiments, the ring C is represented by the formula:

belongs to. In some embodiments, l is 3. In some embodiments, the ring C is represented by the formula:

belongs to. In some embodiments, the ring C is represented by the formula:

belongs to. In some embodiments, the ring C is represented by the formula:

belongs to. In some embodiments, the ring C is represented by the formula:

belongs to. In some embodiments, l is 4. In some embodiments, the ring C is represented by the formula:

belongs to. In some embodiments, the ring C is represented by the formula:

belongs to. In some embodiments, the ring C is represented by the formula:

belongs to. In some embodiments, l is 5. In some embodiments, the ring C is represented by the formula:

belongs to.

である。ある態様において、少なくとも１個のＲ^Ｂは、

である。ある態様において、少なくとも１個のＲ^Ｂは、

である。ある態様において、少なくとも１個のＲ^Ｂは、ブチルである。ある態様において、少なくとも１個のＲ^Ｂは、置換カルボシクリルである。ある態様において、少なくとも１個のＲ^Ｂは、未置換カルボシクリルである。ある態様において、少なくとも１個のＲ^Ｂは、置換ヘテロシクリルである。ある態様において、少なくとも１個のＲ^Ｂは、未置換ヘテロシクリルである。ある態様において、少なくとも１個のＲ^Ｂは、置換ピペリジン（piperidine）である。ある態様において、少なくとも１個のＲ^Ｂは、未置換ピペリジン（piperidine）である。ある態様において、少なくとも１個のＲ^Ｂは、置換ピペリジン（piperizine）である。ある態様において、少なくとも１個のＲ^Ｂは、未置換ピペリジン（piperizine）である。ある態様において、少なくとも１個のＲ^Ｂは、置換ピロリジンである。ある態様において、少なくとも１個のＲ^Ｂは、未置換ピロリジンである。ある態様において、少なくとも１個のＲ^Ｂは、置換モルホリンである。ある態様において、少なくとも１個のＲ^Ｂは、未置換モルホリンである。ある態様において、少なくとも１個のＲ^Ｂは、置換ジアザパン（diazapane）である。ある態様において、少なくとも１個のＲ^Ｂは、未置換ジアザパンである。ある態様において、少なくとも１個のＲ^Ｂは、

である。ある態様において、少なくとも１個のＲ^Ｂは、

である。ある態様において、少なくとも１個のＲ^Ｂは、

である。ある態様において、少なくとも１個のＲ^Ｂは、

である。ある態様において、少なくとも１個のＲ^Ｂは、置換−（ＣＨ_２）（ヘテロシクリル）である。ある態様において、少なくとも１個のＲ^Ｂは、未置換−（ＣＨ_２）（ヘテロシクリル）である。ある態様において、少なくとも１個のＲ^Ｂは、

である。ある態様において、少なくとも１個のＲ^Ｂは、

である。ある態様において、少なくとも１個のＲ^Ｂは、

である。ある態様において、少なくとも１個のＲ^Ｂは、

である。ある態様において、少なくとも１個のＲ^Ｂは、

である。ある態様において、少なくとも１個のＲ^Ｂは、

である。ある態様において、少なくとも１個のＲ^Ｂは、

である。ある態様において、少なくとも１個のＲ^Ｂは、

である。ある態様において、少なくとも１個のＲ^Ｂは、

である。ある態様において、少なくとも１個のＲ^Ｂは、

である。ある態様において、少なくとも１個のＲ^Ｂは、

である。ある態様において、少なくとも１個のＲ^Ｂは、

である。ある態様において、少なくとも１個のＲ^Ｂは、

である。ある態様において、少なくとも１個のＲ^Ｂは、

である。ある態様において、少なくとも１個のＲ^Ｂは、

である。ある態様において、少なくとも１個のＲ^Ｂは、

である。ある態様において、少なくとも１個のＲ^Ｂは、

である。ある態様において、少なくとも１個のＲ^Ｂは、

である。ある態様において、少なくとも１個のＲ^Ｂは、置換−（ＣＨ_２）_２（ヘテロシクリル）である。ある態様において、少なくとも１個のＲ^Ｂは、未置換−（ＣＨ_２）_２（ヘテロシクリル）である。ある態様において、少なくとも１個のＲ^Ｂは、

である。ある態様において、少なくとも１個のＲ^Ｂは、置換−（ＣＨ_２）_３（ヘテロシクリル）である。ある態様において、少なくとも１個のＲ^Ｂは、未置換−（ＣＨ_２）_３（ヘテロシクリル）である。ある態様において、少なくとも１個のＲ^Ｂは、

である。ある態様において、少なくとも１個のＲ^Ｂは、置換アリールである。ある態様において、少なくとも１個のＲ^Ｂは、未置換アリールである。ある態様において、少なくとも１個のＲ^Ｂは、置換フェニルである。ある態様において、少なくとも１個のＲ^Ｂは、未置換フェニルである。ある態様において、少なくとも１個のＲ^Ｂは、置換ヘテロアリールである。ある態様において、少なくとも１個のＲ^Ｂは、未置換ヘテロアリールである。ある態様において、少なくとも１個のＲ^Ｂは、置換ピリジルである。ある態様において、少なくとも１個のＲ^Ｂは、未置換ピリジルである。ある態様において、少なくとも１個のＲ^Ｂは、置換イミダゾールである。ある態様において、少なくとも１個のＲ^Ｂは未置換イミダゾールである。ある態様において、少なくとも１個のＲ^Ｂは、

である。ある態様において、少なくとも１個のＲ^Ｂは、

である。ある態様において、少なくとも１個のＲ^Ｂは、−ＯＲ^Ａ１である。ある態様において、少なくとも１個のＲ^Ｂは、−Ｏ（Ｃ_１−６アルキル）であり、ここで、アルキルは、置換されているかまたは未置換である。ある態様において、少なくとも１個のＲ^Ｂは、−ＯＭｅである。ある態様において、少なくとも１個のＲ^Ｂは、−ＯＰｈである。ある態様において、少なくとも１個のＲ^Ｂは、

である。ある態様において、少なくとも１個のＲ^Ｂは、

である。ある態様において、少なくとも１個のＲ^Ｂは、−ＯＨである。ある態様において、少なくとも１個のＲ^Ｂは、−Ｎ（Ｒ^Ａ１）_２である。ある態様において、少なくとも１個のＲ^Ｂは、−ＮＥｔ_２である。ある態様において、少なくとも１個のＲ^Ｂは、−ＮＭｅ_２である。ある態様において、少なくとも１個のＲ^Ｂは、−ＮＨｔＢｕである。ある態様において、少なくとも１個のＲ^Ｂは、

である。ある態様において、少なくとも１個のＲ^Ｂは、

である。ある態様において、少なくとも１個のＲ^Ｂは、−ＮＨ_２である。ある態様において、少なくとも１個のＲ^Ｂは、−ＣＮである。ある態様において、少なくとも１個のＲ^Ｂは、−Ｃ（＝Ｏ）Ｒ^Ａ１である。ある態様において、少なくとも１個のＲ^Ｂは、アセチルである。ある態様において、少なくとも１個のＲ^Ｂは、−Ｃ（＝Ｏ）ＯＲ^Ａ１である。ある態様において、少なくとも１個のＲ^Ｂは、−Ｃ（＝Ｏ）Ｎ（Ｒ^Ａ１）_２である。ある態様において、少なくとも１個のＲ^Ｂは、−Ｃ（＝Ｏ）ＮＨＲ^Ａ１である。ある態様において、少なくとも１個のＲ^Ｂは、−Ｃ（＝Ｏ）ＮＨ（Ｃ_１−６アルキル）であり、ここで、アルキルは、置換されているかまたは未置換である。ある態様において、少なくとも１個のＲ^Ｂは、−Ｃ（＝Ｏ）ＮＨＭｅである。ある態様において、少なくとも１個のＲ^Ｂは、−Ｃ（＝Ｏ）ＮＨ_２である。ある態様において、少なくとも１個のＲ^Ｂは、

である。ある態様において、少なくとも１個のＲ^Ｂは、

である。ある態様において、少なくとも１個のＲ^Ｂは、−ＮＯ_２である。ある態様において、少なくとも１個のＲ^Ｂは、−ＮＲ^Ａ１Ｃ（＝Ｏ）Ｒ^Ａ１である。ある態様において、少なくとも１個のＲ^Ｂは、−ＮＲ^Ａ１Ｃ（＝Ｏ）ＯＲ^Ａ１である。ある態様において、少なくとも１個のＲ^Ｂは、−ＮＲ^Ａ１Ｓ（＝Ｏ）_２Ｒ^Ａ１である。ある態様において、少なくとも１個のＲ^Ｂは、−ＮＨＳ（＝Ｏ）_２Ｒ^Ａ１である。ある態様において、少なくとも１個のＲ^Ｂは、−ＮＨＳ（＝Ｏ）_２（Ｃ_１−６アルキル）であり、ここで、アルキルは、置換されているかまたは未置換である。ある態様において、少なくとも１個のＲ^Ｂは、−ＮＨＳ（＝Ｏ）_２Ｍｅである。ある態様において、少なくとも１個のＲ^Ｂは、−Ｓ（＝Ｏ）_２Ｒ^Ａ１である。ある態様において、少なくとも１個のＲ^Ｂは、−Ｓ（＝Ｏ）_２Ｎ（Ｒ^Ａ１）_２である。ある態様において、少なくとも１個のＲ^Ｂは、−Ｓ（＝Ｏ）_２Ｎ（Ｒ^Ａ１）_２である。ある態様において、少なくとも１個のＲ^Ｂは、−Ｓ（＝Ｏ）_２Ｎ（Ｃ_１−６アルキル）_２である。ある態様において、少なくとも１個のＲ^Ｂは、−Ｓ（＝Ｏ）_２ＮＨ（Ｃ_１−６アルキル）である。ある態様において、少なくとも１個のＲ^Ｂは、−Ｓ（＝Ｏ）_２ＮＨ（ｔ−Ｂｕ）である。ある態様において、少なくとも１個のＲ^Ｂは、−Ｓ（＝Ｏ）_２ＮＨ_２である。 In compounds of formula (A), ring C may be substituted by one or more of R ^B groups. In certain embodiments, at least one of ^{R B} is H. In certain embodiments, at least two ^{R B} groups are H. In certain embodiments, at least three ^{R B} groups are H. In certain embodiments, at least four ^{R B} groups are H. In certain embodiments, at least one of ^{R B} are not H. In certain embodiments, at least two R ^B groups are not H. In certain embodiments, at least three R ^B groups are not H. In certain embodiments, at least one of R ^B is halogen. In certain embodiments, at least one of ^{R B} is F. In certain embodiments, at least one of ^{R B} is is Cl. In certain embodiments, at least one of ^{R B} is Br. In certain embodiments, at least one of ^{R B} is I (iodine). In certain embodiments, one of ^{R B} is F. In certain embodiments, one of ^{R B} is is Cl. In certain embodiments, at least one of R ^B is substituted alkyl. In certain embodiments, at least one of R ^B is unsubstituted alkyl. In certain embodiments, at least one of ^{R B} is a substituted _{C 1-6} alkyl. In certain embodiments, at least one of ^{R B} is unsubstituted _{C 1-6} alkyl. In certain embodiments, at least one of R ^B is methyl. In certain embodiments, at least one of R ^B is ethyl. In certain embodiments, at least one of R ^B is propyl. In certain embodiments, at least one of ^{R B} is,

Is. In certain embodiments, at least one of ^{R B} is,

Is. In certain embodiments, at least one of ^{R B} is,

Is. In certain embodiments, at least one of R ^B is butyl. In certain embodiments, at least one of R ^B is a substituted carbocyclyl. In certain embodiments, at least one of R ^B is unsubstituted carbocyclyl. In certain embodiments, at least one of R ^B is a substituted heterocyclyl. In certain embodiments, at least one of R ^B is unsubstituted heterocyclyl. In certain embodiments, at least one of R ^B is a substituted piperidine (piperidine). In certain embodiments, at least one of R ^B is unsubstituted piperidine (piperidine). In certain embodiments, at least one of R ^B is a substituted piperidine (piperizine). In certain embodiments, at least one of R ^B is unsubstituted piperidine (piperizine). In certain embodiments, at least one of R ^B is a substituted pyrrolidine. In certain embodiments, at least one of R ^B is unsubstituted pyrrolidine. In certain embodiments, at least one of R ^B is a substituted morpholine. In certain embodiments, at least one of R ^B is unsubstituted morpholine. In certain embodiments, at least one of R ^B is a substituted Jiazapan (diazapane). In certain embodiments, at least one of R ^B is unsubstituted Jiazapan. In certain embodiments, at least one of ^{R B} is,

Is. In certain embodiments, at least one of ^{R B} is,

Is. In certain embodiments, at least one of ^{R B} is,

Is. In certain embodiments, at least one of ^{R B} is,

Is. In certain embodiments, at least one of ^{R B} is substituted - a _(CH 2) (heterocyclyl). In certain embodiments, at least one of ^{R B} is unsubstituted - a _(CH 2) (heterocyclyl). In certain embodiments, at least one of ^{R B} is,

Is. In certain embodiments, at least one of ^{R B} is,

Is. In certain embodiments, at least one of ^{R B} is,

Is. In certain embodiments, at least one of ^{R B} is,

Is. In certain embodiments, at least one of ^{R B} is,

Is. In certain embodiments, at least one of ^{R B} is,

Is. In certain embodiments, at least one of ^{R B} is,

Is. In certain embodiments, at least one of ^{R B} is,

Is. In certain embodiments, at least one of ^{R B} is,

Is. In certain embodiments, at least one of ^{R B} is,

Is. In certain embodiments, at least one of ^{R B} is,

Is. In certain embodiments, at least one of ^{R B} is,

Is. In certain embodiments, at least one of ^{R B} is,

Is. In certain embodiments, at least one of ^{R B} is,

Is. In certain embodiments, at least one of ^{R B} is,

Is. In certain embodiments, at least one of ^{R B} is,

Is. In certain embodiments, at least one of ^{R B} is,

Is. In certain embodiments, at least one of ^{R B} is,

Is. In certain embodiments, at least one of ^{R B} is substituted - a _{(CH 2) 2} (heterocyclyl). In certain embodiments, at least one of ^{R B} is unsubstituted - a _{(CH 2) 2} (heterocyclyl). In certain embodiments, at least one of ^{R B} is,

Is. In certain embodiments, at least one of ^{R B} is substituted - a _{(CH 2) 3} (heterocyclyl). In certain embodiments, at least one of ^{R B} is unsubstituted - a _{(CH 2) 3} (heterocyclyl). In certain embodiments, at least one of ^{R B} is,

Is. In certain embodiments, at least one of R ^B is substituted aryl. In certain embodiments, at least one of R ^B is unsubstituted aryl. In certain embodiments, at least one of R ^B is a substituted phenyl. In certain embodiments, at least one of R ^B is unsubstituted phenyl. In certain embodiments, at least one of R ^B is a substituted heteroaryl. In certain embodiments, at least one of R ^B is unsubstituted heteroaryl. In certain embodiments, at least one of R ^B is a substituted pyridyl. In certain embodiments, at least one of R ^B is unsubstituted pyridyl. In certain embodiments, at least one of R ^B is a substituted imidazole. In certain embodiments, at least one of R ^B is unsubstituted imidazole. In certain embodiments, at least one of ^{R B} is,

Is. In certain embodiments, at least one of ^{R B} is,

Is. In certain embodiments, at least one of ^R B is ^{-OR A1.} In certain embodiments, at least one of ^R B is -O _{(C 1-6} alkyl), wherein alkyl, or is unsubstituted are substituted. In certain embodiments, at least one of ^{R B} is -OMe. In certain embodiments, at least one of ^{R B} is -OPh. In certain embodiments, at least one of ^{R B} is,

Is. In certain embodiments, at least one of ^{R B} is,

Is. In certain embodiments, at least one of ^{R B} is -OH. In certain embodiments, at least one of ^{R B} is ^{-N (R} _{A1) 2.} In certain embodiments, at least one of ^{R B} is -NEt _2. In certain embodiments, at least one of ^{R B} is -NMe _2. In certain embodiments, at least one of ^{R B} is -NHtBu. In certain embodiments, at least one of ^{R B} is,

Is. In certain embodiments, at least one of ^{R B} is,

Is. In certain embodiments, at least one of ^{R B} is -NH _2. In certain embodiments, at least one of ^{R B} is -CN. In certain embodiments, at least one of ^{R B} is -C (= ^{O) R A1.} In certain embodiments, at least one of R ^B is acetyl. In certain embodiments, at least one of ^{R B} is -C (= O) ^{OR A1.} In certain embodiments, at least one of ^{R B} is ^{-C (= O) N (R} A1) 2. In certain embodiments, at least one of ^{R B} is -C (= O) ^{NHR A1.} In certain embodiments, at least one of ^{R B} is _{-C (= O) NH (C} 1-6 alkyl), wherein alkyl, or is unsubstituted are substituted. In certain embodiments, at least one of ^{R B} is -C (= O) NHMe. In certain embodiments, at least one of ^{R B} is -C (= O) NH _2. In certain embodiments, at least one of ^{R B} is,

Is. In certain embodiments, at least one of ^{R B} is,

Is. In certain embodiments, at least one of ^{R B} is -NO _2. In certain embodiments, at least one of ^{R B is -NR A1 C (= O) R} A1. In certain embodiments, at least one of ^{R B is -NR A1 C (= O) OR} A1. In certain embodiments, at least one of ^{R B is _{-NR A1 S (= O) 2}} R A1. In certain embodiments, at least one of ^{R B} is ^{_{-NHS (= O) 2 R A1}} . In certain embodiments, at least one of ^{R B} is _{-NHS (= O) 2 (C} 1-6 alkyl), wherein alkyl, or is unsubstituted are substituted. In certain embodiments, at least one of ^{R B} is -NHS (= _O) 2 Me. In certain embodiments, at least one of ^{R B} is ^{_{-S (= O) 2 R A1}} . In certain embodiments, at least one of ^R B is ^{_{-S (= O) 2 N (}} R A1) 2. In certain embodiments, at least one of ^R B is ^{_{-S (= O) 2 N (}} R A1) 2. In certain embodiments, at least one of ^R B is _{-S (= O) 2 N (} C 1-6 _{alkyl) 2.} In certain embodiments, at least one of ^R B is _{-S (= O) 2 NH (} C 1-6 alkyl). In certain embodiments, at least one of ^R B is _{-S (= O) 2 NH (} t-Bu). In certain embodiments, at least one of ^{R B} is _{-S (= O) 2 NH 2} .

であり；ｌは１である。ある態様において、Ｒ^Ｂは、

であり；ｌは１であり；Ｒ^Ｂは、Ｕの結合点に対してメタ位にある。ある態様において、Ｒ^Ｂは、

であり；ｌは１であり；Ｒ^Ｂは、Ｕの結合点に対してパラ位にある。ある態様において、Ｒ^Ｂは、置換または未置換−ＣＨ_２−（ピペラジニル）であり；ｌは１である。ある態様において、Ｒ^Ｂは、置換または未置換−ＣＨ_２−（ピペラジニル）であり；ｌは１であり；Ｒ^Ｂは、Ｕの結合点に対してメタ位にある。ある態様において、Ｒ^Ｂは、置換または未置換−ＣＨ_２−（ピペラジニル）であり；ｌは１であり；Ｒ^Ｂは、Ｕの結合点に対してパラ位にある。ある態様において、Ｒ^Ｂは、

であり；ｌは１である。ある態様において、Ｒ^Ｂは、

であり；ｌは１であり；Ｒ^Ｂは、Ｕの結合点に対してメタ位にある。ある態様において、Ｒ^Ｂは、

であり；ｌは１であり；Ｒ^Ｂは、Ｕの結合点に対してパラ位にある。ある態様において、Ｒ^Ｂはハロアルキルであり；ｌは１である。ある態様において、Ｒ^Ｂはハロアルキルであり；ｌは１であり；Ｒ^Ｂは、Ｕの結合点に対してメタ位にある。ある態様において、Ｒ^Ｂはハロアルキルであり；ｌは１であり；Ｒ^Ｂは、Ｕの結合点に対してパラ位にある。ある態様において、Ｒ^Ｂは−ＣＦ_３であり；ｌは１である。ある態様において、Ｒ^Ｂは−ＣＦ_３であり；ｌは１であり；Ｒ^Ｂは、Ｕの結合点に対してメタ位にある。ある態様において、Ｒ^Ｂは−ＣＦ_３であり；ｌは１であり；Ｒ^Ｂは、Ｕの結合点に対してパラ位にある。ある態様において、Ｒ^Ｂは、置換または未置換イミダゾリルであり；ｌは１である。ある態様において、Ｒ^Ｂは、置換または未置換イミダゾリルであり；ｌは１であり；Ｒ^Ｂは、Ｕの結合点に対してメタ位にある。ある態様において、Ｒ^Ｂは、置換または未置換イミダゾリルであり；ｌは１であり；Ｒ^Ｂは、Ｕの結合点に対してパラ位にある。ある態様において、Ｒ^Ｂは、

であり；ｌは１である。ある態様において、Ｒ^Ｂは、

であり；ｌは１であり；Ｒ^Ｂは、Ｕの結合点に対してメタ位にある。ある態様において、Ｒ^Ｂは、

であり；ｌは１であり；Ｒ^Ｂは、Ｕの結合点に対してパラ位にある。ある態様において、Ｒ^Ｂは、置換または未置換ピペラジニルであり；ｌは１である。ある態様において、Ｒ^Ｂは、置換または未置換ピペラジニルであり；ｌは１であり；Ｒ^Ｂは、Ｕの結合点に対してメタ位にある。ある態様において、Ｒ^Ｂは、置換または未置換ピペラジニルであり；ｌは１であり；Ｒ^Ｂは、Ｕの結合点に対してパラ位にある。ある態様において、Ｒ^Ｂは、

であり；ｌは１である。ある態様において、Ｒ^Ｂは、

であり；ｌは１であり；Ｒ^Ｂは、Ｕの結合点に対してメタ位にある。ある態様において、Ｒ^Ｂは、

であり；ｌは１であり；Ｒ^Ｂは、Ｕの結合点に対してパラ位にある。ある態様において、Ｒ^Ｂは、置換または未置換モルホリンであり；ｌは１である。ある態様において、Ｒ^Ｂは、置換または未置換モルホリンであり；ｌは１であり；Ｒ^Ｂは、Ｕの結合点に対してメタ位にある。ある態様において、Ｒ^Ｂは、置換または未置換モルホリンであり；ｌは１であり；Ｒ^Ｂは、Ｕの結合点に対してパラ位にある。 In certain embodiments, ^{R B} is a substituted or unsubstituted _{C 1-6} alkyl; l is 1. In certain embodiments, ^{R B} is a substituted or unsubstituted _{C 1-6} alkyl; l is an 1; ^{R B} is meta to the point of attachment of the U. In certain embodiments, ^{R B} is a substituted or unsubstituted _{C 1-6} alkyl; l is an 1; ^{R B} is in the para position relative to the point of attachment of the U. In certain embodiments, ^{R B} is an _{C 1-6} alkyl substituted with one -CN group; l is 1. In certain embodiments, ^{R B} is located with one _{C 1-6} alkyl substituted with -CN group; l is 1; ^{R B} is meta to the point of attachment of the U. In certain embodiments, ^{R B} is located with one _{C 1-6} alkyl substituted with -CN group; l is 1; ^{R B} is in the para position relative to the point of attachment of the U. In certain embodiments, ^{R B} is,

Is; l is 1. In certain embodiments, ^{R B} is,

In it; l is an 1; R ^B is meta to the point of attachment of the U. In certain embodiments, ^{R B} is,

In it; l is an 1; R ^B is in the para position relative to the point of attachment of the U. In certain embodiments, ^{R B} is a substituted or unsubstituted -CH ₂ - be (piperazinyl); l is 1. In certain embodiments, ^{R B} is a substituted or unsubstituted -CH ₂ - be (piperazinyl); l is an 1; ^{R B} is meta to the point of attachment of the U. In certain embodiments, ^{R B} is a substituted or unsubstituted -CH ₂ - be (piperazinyl); l is an 1; ^{R B} is in the para position relative to the point of attachment of the U. In certain embodiments, ^{R B} is,

Is; l is 1. In certain embodiments, ^{R B} is,

In it; l is an 1; R ^B is meta to the point of attachment of the U. In certain embodiments, ^{R B} is,

In it; l is an 1; R ^B is in the para position relative to the point of attachment of the U. In certain embodiments, ^{R B} is a haloalkyl; l is 1. In certain embodiments, R ^B is a haloalkyl; l is an 1; R ^B is meta to the point of attachment of the U. In certain embodiments, R ^B is a haloalkyl; l is an 1; R ^B is in the para position relative to the point of attachment of the U. In certain embodiments, ^{R B} is an -CF _3; l is 1. In certain embodiments, ^{R B} is an -CF _3; l is an 1; ^{R B} is meta to the point of attachment of the U. In certain embodiments, ^{R B} is an -CF _3; l is an 1; ^{R B} is in the para position relative to the point of attachment of the U. In certain embodiments, R ^B is a substituted or unsubstituted imidazolyl; l is 1. In certain embodiments, R ^B is a substituted or unsubstituted imidazolyl; l is an 1; R ^B is meta to the point of attachment of the U. In certain embodiments, R ^B is a substituted or unsubstituted imidazolyl; l is an 1; R ^B is in the para position relative to the point of attachment of the U. In certain embodiments, ^{R B} is,

Is; l is 1. In certain embodiments, ^{R B} is,

In it; l is an 1; R ^B is meta to the point of attachment of the U. In certain embodiments, ^{R B} is,

In it; l is an 1; R ^B is in the para position relative to the point of attachment of the U. In certain embodiments, R ^B is a substituted or unsubstituted piperazinyl; l is 1. In certain embodiments, R ^B is a substituted or unsubstituted piperazinyl; l is an 1; R ^B is meta to the point of attachment of the U. In certain embodiments, R ^B is a substituted or unsubstituted piperazinyl; l is an 1; R ^B is in the para position relative to the point of attachment of the U. In certain embodiments, ^{R B} is,

Is; l is 1. In certain embodiments, ^{R B} is,

In it; l is an 1; R ^B is meta to the point of attachment of the U. In certain embodiments, ^{R B} is,

In it; l is an 1; R ^B is in the para position relative to the point of attachment of the U. In certain embodiments, R ^B is a substituted or unsubstituted morpholine; l is 1. In certain embodiments, R ^B is a substituted or unsubstituted morpholine; l is an 1; R ^B is meta to the point of attachment of the U. In certain embodiments, R ^B is a substituted or unsubstituted morpholine; l is an 1; R ^B is in the para position relative to the point of attachment of the U.

であり；ｌは２である。ある態様において、少なくとも１個のＲ^Ｂ基は、

であり；ｌは２であり；少なくとも１個のＲ^Ｂは、Ｕの結合点に対してメタ位にある。ある態様において、少なくとも１個のＲ^Ｂ基は、

であり；ｌは２であり；１個のＲ^Ｂは、Ｕの結合点に対してパラ位にある。ある態様において、少なくとも１個のＲ^Ｂ基は、置換または未置換−ＣＨ_２−（ピペラジニル）であり；ｌは２である。ある態様において、少なくとも１個のＲ^Ｂ基は、置換または未置換−ＣＨ_２−（ピペラジニル）であり；ｌは２であり；少なくとも１個のＲ^Ｂは、Ｕの結合点に対してメタ位にある。ある態様において、少なくとも１個のＲ^Ｂ基は、置換または未置換−ＣＨ_２−（ピペラジニル）であり；ｌは２であり；１個のＲ^Ｂは、Ｕの結合点に対してパラ位にある。ある態様において、少なくとも１個のＲ^Ｂ基は、

であり；ｌは２である。ある態様において、少なくとも１個のＲ^Ｂ基は、

であり；ｌは２であり；少なくとも１個のＲ^Ｂは、Ｕの結合点に対してメタ位にある。ある態様において、少なくとも１個のＲ^Ｂ基は、

であり；ｌは２であり；１個のＲ^Ｂは、Ｕの結合点に対してパラ位にある。ある態様において、少なくとも１個のＲ^Ｂ基はハロアルキルであり；ｌは２である。ある態様において、少なくとも１個のＲ^Ｂ基はハロアルキルであり；ｌは２であり；少なくとも１個のＲ^Ｂは、Ｕの結合点に対してメタ位にある。ある態様において、少なくとも１個のＲ^Ｂ基はハロアルキルであり；ｌは２であり；１個のＲ^Ｂは、Ｕの結合点に対してパラ位にある。ある態様において、少なくとも１個のＲ^Ｂ基は、−ＣＦ_３であり；ｌは２である。ある態様において、少なくとも１個のＲ^Ｂ基は、−ＣＦ_３であり；ｌは２であり；少なくとも１個のＲ^Ｂは、Ｕの結合点に対してメタ位にある。ある態様において、少なくとも１個のＲ^Ｂ基は、−ＣＦ_３であり；ｌは２であり；１個のＲ^Ｂは、Ｕの結合点に対してパラ位にある。ある態様において、少なくとも１個のＲ^Ｂ基は、置換または未置換イミダゾリルであり；ｌは２である。ある態様において、少なくとも１個のＲ^Ｂ基は、置換または未置換イミダゾリルであり；ｌは２であり；少なくとも１個のＲ^Ｂは、Ｕの結合点に対してメタ位にある。ある態様において、少なくとも１個のＲ^Ｂ基は、置換または未置換イミダゾリルであり；ｌは２であり；１個のＲ^Ｂは、Ｕの結合点に対してパラ位にある。ある態様において、少なくとも１個のＲ^Ｂ基は、

であり；ｌは２である。ある態様において、少なくとも１個のＲ^Ｂ基は、

であり；ｌは２であり；少なくとも１個のＲ^Ｂは、Ｕの結合点に対してメタ位にある。ある態様において、少なくとも１個のＲ^Ｂ基は、

であり；ｌは２であり；１個のＲ^Ｂは、Ｕの結合点に対してパラ位にある。ある態様において、少なくとも１個のＲ^Ｂ基は、置換または未置換ピペラジニルであり；ｌは２である。ある態様において、少なくとも１個のＲ^Ｂ基は、置換または未置換ピペラジニルであり；ｌは２であり；少なくとも１個のＲ^Ｂは、Ｕの結合点に対してメタ位にある。ある態様において、少なくとも１個のＲ^Ｂ基は、置換または未置換ピペラジニルであり；ｌは２であり；１個のＲ^Ｂは、Ｕの結合点に対してパラ位にある。ある態様において、少なくとも１個のＲ^Ｂ基は、

であり；ｌは２である。ある態様において、少なくとも１個のＲ^Ｂ基は、

であり；ｌは２であり；少なくとも１個のＲ^Ｂは、Ｕの結合点に対してメタ位にある。ある態様において、少なくとも１個のＲ^Ｂ基は、

であり；ｌは２であり；１個のＲ^Ｂは、Ｕの結合点に対してパラ位にある。ある態様において、少なくとも１個のＲ^Ｂ基は、置換または未置換モルホリンであり；ｌは２である。ある態様において、少なくとも１個のＲ^Ｂ基は、置換または未置換モルホリンであり；ｌは２であり；少なくとも１個のＲ^Ｂは、Ｕの結合点に対してメタ位にある。ある態様において、少なくとも１個のＲ^Ｂ基は、置換または未置換モルホリンであり；ｌは２であり；１個のＲ^Ｂは、Ｕの結合点に対してパラ位にある。ある態様において、２個のＲ^Ｂ基は、置換または未置換モルホリンであり；ｌは２であり；両方のＲ^Ｂ基は、Ｕの結合点に対してメタ位にある。 In certain embodiments, at least one of ^{R B} group, a substituted or unsubstituted _{C 1-6} alkyl; l is 2. In certain embodiments, at least one of R ^B group, a substituted or unsubstituted C _1-6 alkyl; l is 2; at least one of R ^B is meta to the point of attachment of the U .. In certain embodiments, at least one of R ^B group, a substituted or unsubstituted C _1-6 alkyl; l is 2; one R ^B is in the para position relative to the point of attachment of the U. In certain embodiments, at least one of ^{R B} groups is an _{C 1-6} alkyl substituted with one -CN group; l is 2. In certain embodiments, at least one of ^{R B} groups is an one _{C 1-6} alkyl substituted with -CN group; l is 2; at least one of ^{R B} is the point of attachment of the U On the other hand, it is in the meta position. In certain embodiments, at least one of ^{R B} groups is an one _{C 1-6} alkyl substituted with -CN group; l is 2; one ^{R B,} compared point of attachment of the U It is in the para position. In certain embodiments, at least one of ^{R B} group,

Is; l is 2. In certain embodiments, at least one of ^{R B} group,

In it, l is 2, at least one of R ^B is meta to the point of attachment of the U. In certain embodiments, at least one of ^{R B} group,

In it, l is 2; one R ^B is in the para position relative to the point of attachment of the U. In certain embodiments, at least one of ^{R B} group, a substituted or unsubstituted -CH ₂ - be (piperazinyl); l is 2. In certain embodiments, at least one of ^{R B} group, a substituted or unsubstituted -CH ₂ - be (piperazinyl); l is 2; at least one of ^{R B} is meta to the point of attachment of the U It is in. In certain embodiments, at least one of ^{R B} group, a substituted or unsubstituted -CH ₂ - be (piperazinyl); l is 2; one ^{R B} is in the para position relative to the point of attachment of the U is there. In certain embodiments, at least one of ^{R B} group,

Is; l is 2. In certain embodiments, at least one of ^{R B} group,

In it, l is 2, at least one of R ^B is meta to the point of attachment of the U. In certain embodiments, at least one of ^{R B} group,

In it, l is 2; one R ^B is in the para position relative to the point of attachment of the U. In certain embodiments, at least one of R ^B groups is haloalkyl; l is 2. In certain embodiments, at least one of R ^B groups is haloalkyl; l is 2; at least one of R ^B, is in the meta position relative to the point of attachment of the U. In certain embodiments, at least one of R ^B groups is haloalkyl; l is 2; one R ^B is in the para position relative to the point of attachment of the U. In certain embodiments, at least one of ^{R B} groups is an -CF _3; l is 2. In certain embodiments, at least one of ^{R B} groups is an -CF _3; l is 2; at least one of ^{R B} is meta to the point of attachment of the U. In certain embodiments, at least one of ^{R B} groups is an -CF _3; l is 2; one ^{R B} is in the para position relative to the point of attachment of the U. In certain embodiments, at least one of R ^B group, a substituted or unsubstituted imidazolyl; l is 2. In certain embodiments, at least one of R ^B group, a substituted or unsubstituted imidazolyl; l is 2; at least one of R ^B is meta to the point of attachment of the U. In certain embodiments, at least one of R ^B group, a substituted or unsubstituted imidazolyl; l is 2; one R ^B is in the para position relative to the point of attachment of the U. In certain embodiments, at least one of ^{R B} group,

Is; l is 2. In certain embodiments, at least one of ^{R B} group,

In it, l is 2, at least one of R ^B is meta to the point of attachment of the U. In certain embodiments, at least one of ^{R B} group,

In it, l is 2; one R ^B is in the para position relative to the point of attachment of the U. In certain embodiments, at least one of R ^B group, a substituted or unsubstituted piperazinyl; l is 2. In certain embodiments, at least one of R ^B group, a substituted or unsubstituted piperazinyl; l is 2; at least one of R ^B is meta to the point of attachment of the U. In certain embodiments, at least one of R ^B group, a substituted or unsubstituted piperazinyl; l is 2; one R ^B is in the para position relative to the point of attachment of the U. In certain embodiments, at least one of ^{R B} group,

Is; l is 2. In certain embodiments, at least one of ^{R B} group,

In it, l is 2, at least one of R ^B is meta to the point of attachment of the U. In certain embodiments, at least one of ^{R B} group,

In it, l is 2; one R ^B is in the para position relative to the point of attachment of the U. In certain embodiments, at least one of R ^B group, a substituted or unsubstituted morpholine; l is 2. In certain embodiments, at least one of R ^B group, a substituted or unsubstituted morpholine; l is 2; at least one of R ^B is meta to the point of attachment of the U. In certain embodiments, at least one of R ^B group, a substituted or unsubstituted morpholine; l is 2; one R ^B is in the para position relative to the point of attachment of the U. In some embodiments, two R ^B groups is a substituted or unsubstituted morpholine; l is 2; both R ^B groups are in the meta position relative to the point of attachment of the U.

を表す。ある態様において、ＱとＵとは、一緒にされて、

を表す。ある態様において、ＱとＵとは、一緒にされて、

を表す。ある態様において、ＱとＵとは、一緒にされて、

を表す。 In the compound of formula (A), Q and U are combined to represent a divalent linker moiety. In some embodiments, Q and U are combined and

Represents. In some embodiments, Q and U are combined and

Represents. In some embodiments, Q and U are combined and

Represents. In some embodiments, Q and U are combined and

Represents.

である。ある態様において、環Ｂの式は

である。ある態様において、環Ｂの式は

である。ある態様において、環Ｂの式は

である。ある態様において、環Ｂの式は、

である。 Formula (A) comprises a pyridine or pyrimidine ring as ring B. In some embodiments, each case of A contained in ring B is carbon. In some embodiments, one A contained in ring B is carbon and another A contained in ring B is nitrogen. In some embodiments, the equation for ring B is

Is. In some embodiments, the equation for ring B is

Is. In some embodiments, the equation for ring B is

Is. In some embodiments, the equation for ring B is

Is. In some embodiments, the equation for ring B is

Is.

Formula (A) may comprise one or more ^{R Y.} Formula (A) is, when comprising two R ^Y, the two R ^Y may be the same or different from each other. In some embodiments, at least one ^RY is H. In some embodiments, each ^RY is H. In some embodiments, at least one ^RY is a halogen (eg, F, Cl, Br, or I). In some embodiments, at least one ^RY is a substituted or unsubstituted C _1-6 alkyl. In some embodiments, at least one ^RY is Me. In some embodiments, at least one ^RY is a substituted methyl (eg, -CF ₃ or Bn). In some embodiments, the at least one ^RY is Et, substituted ethyl, (eg, perfluoroethyl), Pr, substituted propyl (eg, perfluoropropyl), Bu, or substituted butyl (eg, perfluorobutyl). ..

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、置換ヘテロシクリルである。ある態様において、少なくとも１個のＲ^Ｘは、未置換ヘテロシクリルである。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、置換アリールである。ある態様において、少なくとも１個のＲ^Ｘは、未置換アリールである。ある態様において、少なくとも１個のＲ^Ｘは、置換フェニルである。ある態様において、少なくとも１個のＲ^Ｘは、未置換フェニルである。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において少なくとも１個のＲ^Ｘは置換へテロアリールである。ある態様において、少なくとも１個のＲ^Ｘは未置換へテロアリールである。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、−Ｎ（Ｒ^Ａ１）（Ｒ^Ｘａ）である。ある態様において、少なくとも１個のＲ^Ｘは、−ＮＨ_２である。ある態様において、少なくとも１個のＲ^Ｘは、−ＮＨ（３−６員シクロアルキル）であり、ここで当該シクロアルキルは置換または未置換である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、−ＮＨ（Ｃ_１−６アルキル）であり、ここで当該アルキルは、置換または未置換である。ある態様において、少なくとも１個のＲ^Ｘは、−ＮＨ（Ｃ_１−６アルキル）_２であり、ここで当該アルキルは、置換または未置換である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、−ＮＨ（アシル）である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、−ＮＨＣ（＝Ｏ）（３−６員シクロアルキル）であり、ここで当該シクロアルキルは置換または未置換である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、−ＮＨＣ（＝Ｏ）（Ｃ_１−６アルキル）であり、ここで当該アルキルは置換または未置換である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは、

である。ある態様において、少なくとも１個のＲ^Ｘは−Ｎ（Ｒ^Ａ１）Ｎ（Ｒ^Ａ１）_２である。ある態様において、少なくとも１個のＲ^Ｘは−ＮＨＮ（Ｒ^Ａ１）_２である。ある態様において、少なくとも１個のＲ^Ｘは−ＮＨＮＨ（アシル）である。ある態様において、少なくとも１個のＲ^Ｘは−ＮＨＮＨＣ（＝Ｏ）Ｍｅである。ある態様において、少なくとも１個のＲ^Ｘは、−ＮＨＮ（Ｃ_１−６アルキル）_２であり、ここで当該アルキルは置換または未置換である。ある態様において、少なくとも１個のＲ^Ｘは−ＮＨＮＭｅ_２である。 In the compound of formula (A), the pyridine ring or the pyrimidine ring may be substituted with ^{one or more RX groups.} When the formula (A) contains two R ^X, the two R ^X may be the same or different from each other. In some embodiments, at least one R ^X, is a substituted carbocyclyl. In certain embodiments, at least one R ^X is an unsubstituted carbocyclyl. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In some embodiments, at least one R ^X, is a substituted heterocyclyl. In certain embodiments, at least one R ^X is an unsubstituted heterocyclyl. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In some embodiments, at least one R ^X, is a substituted aryl. In certain embodiments, at least one R ^X is an unsubstituted aryl. In some embodiments, at least one R ^X, is a substituted phenyl. In certain embodiments, at least one R ^X is an unsubstituted phenyl. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. At least one R ^X In some embodiments is substituted heteroaryl. In certain embodiments, at least one R ^X is heteroaryl unsubstituted. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In some embodiments, at least one ^{R X,} is ^{-N (R A1) (R Xa} ). In some embodiments, at least one ^{R X,} is -NH _2. In some embodiments, at least one R ^X, is -NH (3-6 membered cycloalkyl), wherein said cycloalkyl is substituted or unsubstituted. In certain embodiments, at least one ^{R X} is

Is. In some embodiments, at least one ^{R X,} is -NH _{(C 1-6} alkyl), wherein said alkyl is substituted or unsubstituted. In some embodiments, at least one ^{R X,} is -NH _{(C 1-6 alkyl) 2,} wherein said alkyl is substituted or unsubstituted. In certain embodiments, at least one ^{R X} is

Is. In some embodiments, at least one ^{R X,} is -NH (acyl). In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In some embodiments, at least one ^{R X,} is a -NHC (= O) (3-6 membered cycloalkyl), wherein said cycloalkyl is substituted or unsubstituted. In certain embodiments, at least one ^{R X} is

Is. In some embodiments, at least one ^{R X,} is a -NHC _{(= O) (C 1-6} alkyl), wherein said alkyl is substituted or unsubstituted. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is

Is. In certain embodiments, at least one ^{R X} is ^{-N (R A1) N (R} A1) 2. In certain embodiments, at least one ^{R X} is -NHN ^(R _{A1) 2.} In certain embodiments, at least one ^{R X} is -NHNH (acyl). In certain embodiments, at least one ^{R X} is -NHNHC (= O) Me. In some embodiments, at least one ^{R X,} is -NHN _{(C 1-6 alkyl) 2,} wherein said alkyl is substituted or unsubstituted. In certain embodiments, at least one ^{R X} is -NHNMe _2.

In the compounds of formula (A), R ^X may be substituted with one or two or more R ^Xa groups. In ^{each case of RXa} , hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, -C (= O) ^RA1 , -C (= O) OR ^A1 , -C (= O) N ( ^RA1 ) ₂ , -S (= O) ^RA1 , -S (= O) N ( ^RA1 ) ₂ ,- Select from the group consisting of S (= O) ₂ ^RA1 , -S (= O) ₂ OR ^A1 , -S (= O) ₂ N ( ^RA1 ) ₂ , -N ( ^RA1 ) _{2, and nitrogen protecting groups.} by; wherein each occurrence of R ^A1 is independently hydrogen, optional substituted acyl, the optionally substituted alkyl, the optionally substituted alkenyl, arbitrary substituted alkynyl, any substitution carbocyclyl, any substituted heterocyclyl, optionally substituted Consists of an aryl, an arbitrarily substituted heteroaryl, a nitrogen protecting group when bonded to a nitrogen atom, an oxygen protecting group when bonded to an oxygen atom, and a sulfur protecting group when bonded to a sulfur atom. Selected from the group or two ^RA1 groups are linked to form an arbitrarily substituted heterocyclic ring.

In some embodiments, at least one ^RXa is H. In some embodiments, all ^RXa groups are H. In some embodiments, at least one ^RXa is a substituted alkyl. In some embodiments, at least one ^RXa is a substituted C _1-6 alkyl. In some embodiments, at least one ^RXa is a substituted methyl. In some embodiments, at least one ^RXa is an unsubstituted alkyl. In some embodiments, at least one ^RXa is an unsubstituted C _1-6 alkyl. In some embodiments, at least one ^RXa is methyl. In some embodiments, at least one ^RXa is ethyl. In some embodiments, at least one ^RXa is propyl. In some embodiments, at least one ^RXa is butyl. In some embodiments, at least one ^RXa is a substituted alkenyl. In some embodiments, at least one ^RXa is an unsubstituted alkenyl. In some embodiments, at least one ^RXa is a substituted alkynyl. In some embodiments, at least one ^RXa is an unsubstituted alkynyl. In some embodiments, at least one ^RXa is a substituted carbocyclyl. In some embodiments, at least one ^RXa is an unsubstituted carbocyclyl. In some embodiments, at least one ^RXa is a substituted heterocyclyl. In some embodiments, at least one ^RXa is an unsubstituted heterocyclyl. In some embodiments, at least one ^RXa is a substituted aryl. In some embodiments, at least one ^RXa is an unsubstituted aryl. In some embodiments, at least one ^RXa is a substituted phenyl. In some embodiments, at least one ^RXa is an unsubstituted phenyl. In some embodiments, at least one ^RXa is a substituted heteroaryl. In some embodiments, at least one ^RXa is an unsubstituted heteroaryl. In some embodiments, at least one ^RXa is -C (= O) ^RA1 . In some embodiments, at least one ^RXa is -C (= O) H. In some embodiments, at least one ^RXa is acetyl. In some embodiments, at least one ^RXa is -C (= O) (C _1-6 alkyl). In some embodiments, at least one ^RXa is -C (= O) OR ^A1 . In some embodiments, at least one ^RXa is -C (= O) OH. In some embodiments, at least one ^RXa is -C (= O) O (C _1-6 alkyl). In some embodiments, at least one ^RXa is -C (= O) N ( ^RA1 ) ₂ . In some embodiments, at least one ^RXa is -C (= O) NHR ^A1 . In some embodiments, at least one ^RXa is -C (= O) N (C _1-6 alkyl) ₂ . In some embodiments, at least one ^RXa is -C (= O) NH (C _1-6 alkyl). In some embodiments, at least one ^RXa is -C (= O) NH ₂ . In some embodiments, at least one ^RXa is -S (= O) ^RA1 . In some embodiments, at least one ^RXa is -S (= O) (C _1-6 alkyl). In some embodiments, at least one ^RXa is -S (= O) N ( ^RA1 ) ₂ . In some embodiments, at least one ^RXa is -S (= O) NH ( ^RA1 ). In some embodiments, at least one ^RXa is -S (= O) NH ₂ . In some embodiments, at least one ^RXa is -S (= O) N (C _1-6 alkyl) ₂ . In some embodiments, at least one ^RXa is -S (= O) NH (C _1-6 alkyl). In some embodiments, at least one ^{R Xa,} a ^{_{-S (= O) 2 R A1}} . In some embodiments, at least one ^RXa is -S (= O) ₂ (C _1-6 alkyl). In some embodiments, at least one ^RXa is -S (= O) ₂ OR ^A1 . In some embodiments, at least one ^RXa is -S (= O) ₂ OH. In some embodiments, at least one ^RXa is -S (= O) ₂ N ( ^RA1 ) ₂ . In some embodiments, at least one ^RXa is -S (= O) ₂ NH ( ^RA1 ). In some embodiments, at least one ^RXa is -S (= O) ₂ NH ₂ . In some embodiments, at least one ^RXa is -S (= O) ₂ N (C _1-6 alkyl) ₂ . In some embodiments, at least one ^RXa is -S (= O) ₂ NH (C _1-6 alkyl). In certain embodiments, at least one ^{R X} is ^{-N (R} _{A1) 2.} In some embodiments, at least one ^RXa is -NH ( ^RA1 ). In some embodiments, at least one ^RXa is -NH (acyl). In some embodiments, at least one ^RXa is -NHC (= O) Me. In some embodiments, at least one ^{R Xa,} a -NHN _{(C 1-6 alkyl) 2,} wherein said alkyl is substituted or unsubstituted. In certain embodiments, at least one of ^{R Xa} is -NMe _2.

In the compounds of formula (A), R ^X may be substituted with one or two or more R ^Xc groups. In ^{each case of RXc} , hydrogen, halogen, optionally substituted alkyl, optionally substituted alkynyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, -OR _{^{A1, -N (R A1) 2}} , -SR A1, -CN, -C (= O) R A1, -C (= O) OR A1, -C (= O) N (R A1) 2, -NO ₂ , -N ₃ , -NR ^A1 C (= O) R ^A1 , -NR ^A1 C (= O) OR ^A1 , -NR ^A1 C (= O) N ( ^RA1 ) ₂ , -NR ^A1 S (= O) ) ₂ R ^A1 , -NR ^A1 S (= O) R ^A1 , -OC (= O) R ^A1 , -OC (= O) OR ^A1 , -OC (= O) N ( ^RA1 ) ₂ , -S ( Selected from the group consisting of = O) R ^A1 , -S (= O) N ( ^RA1 ) ₂ , -S (= O) ₂ R ^A1 , -S (= O) ₂ N ( ^RA1 ) _2; in each occurrence of R ^A1 is independently hydrogen, optional substituted acyl, the optionally substituted alkyl, the optionally substituted alkenyl, arbitrary substituted alkynyl, any substituted carbocyclyl, optionally substituted heterocyclyl, any substituted aryl, Select from the group consisting of an arbitrarily substituted heteroaryl, a nitrogen protecting group when bonded to a nitrogen atom, an oxygen protecting group when bonded to an oxygen atom, and a sulfur protecting group when bonded to a sulfur atom. Or the two ^RA1 groups are linked to form an arbitrarily substituted heterocyclic ring.

In some embodiments, at least one ^RXc is H. In some embodiments, all ^RXc groups are H. In some embodiments, at least one ^RXc is a substituted alkyl. In some embodiments, at least one ^RXc is a substituted C _1-6 alkyl. In some embodiments, at least one ^RXc is a substituted methyl. In some embodiments, at least one ^RXc is an unsubstituted alkyl. In some embodiments, at least one ^RXc is an unsubstituted C _1-6 alkyl. In some embodiments, at least one ^RXc is methyl. In some embodiments, at least one ^RXc is ethyl. In some embodiments, at least one ^RXc is propyl. In some embodiments, at least one ^RXc is butyl. In some embodiments, at least one ^RXc is a substituted alkenyl. In some embodiments, at least one ^RXc is an unsubstituted alkenyl. In some embodiments, at least one ^RXc is a substituted alkynyl. In some embodiments, at least one ^RXc is an unsubstituted alkynyl. In some embodiments, at least one ^RXc is a substituted carbocyclyl. In some embodiments, at least one ^RXc is an unsubstituted carbocyclyl. In some embodiments, at least one ^RXc is a substituted heterocyclyl. In some embodiments, at least one ^RXc is an unsubstituted heterocyclyl. In some embodiments, at least one ^RXc is a substituted aryl. In some embodiments, at least one ^RXc is an unsubstituted aryl. In some embodiments, at least one ^RXc is a substituted phenyl. In some embodiments, at least one ^RXc is an unsubstituted phenyl. In some embodiments, at least one ^RXc is a substituted heteroaryl. In some embodiments, at least one ^RXc is an unsubstituted heteroaryl. In some embodiments, at least one ^RXc is -OR ^A1 . In some embodiments, at least one ^RXc is −OH. In some embodiments, at least one ^RXc is -O (C _1-6 alkyl). In certain embodiments, at least one of ^{R Xc} is ^{-N (R} _{A1) 2.} In some embodiments, at least one ^{R Xc,} is -NH ^{(R A1).} In some embodiments, at least one ^RXc is -N (C _1-6 alkyl) ₂ . In some embodiments, at least one ^RXc is -NH (C _1-6 alkyl). In some embodiments, at least one ^RXc is -NH ₂ . In some embodiments, at least one ^RXc is -SR ^A1 . In some embodiments, at least one ^RXc is -SH. In some embodiments, at least one ^RXc is -S (C _1-6 alkyl). In some embodiments, at least one ^RXc is -CN. In some embodiments, at least one ^RXc is -NO ₂ . In some embodiments, at least one ^RXc is -N ₃ . In some embodiments, at least one ^{R Xc,} is ^{-NR A1 C (= O) R} A1. In some embodiments, at least one ^{R Xc,} is -NHC (= ^{O) R A1.} In some embodiments, at least one ^RXc is -NHC (= O) (C _1-6 alkyl). In some embodiments, at least one ^RXc is -NR ^A1 C (= O) OR ^A1 . In some embodiments, at least one ^RXc is -NHC (= O) OR ^A1 . In some embodiments, at least one ^RXc is -NR ^A1 C (= O) O (C _1-6 alkyl). In some embodiments, at least one ^RXc is -NR ^A1 C (= O) N ( ^RA1 ) ₂ . In some embodiments, at least one ^RXc is -NHC (= O) N (C _1-6 alkyl) ₂ . In some embodiments, at least one ^RXc is -NHC (= O) NH ₂ . In some embodiments, at least one ^RXc is -NR ^A1 S (= O) ₂ ^RA1 . In some embodiments, at least one ^{R Xc,} is ^{_{-NHS (= O) 2 R A1}} . In some embodiments, at least one ^RXc is -NHS (= O) ₂ (C _1-6 alkyl). In some embodiments, at least one ^{R Xc,} is ^{-NR A1 S (= O) R} A1. In some embodiments, at least one ^RXc is -NR ^A1 S (= O) (C _1-6 alkyl). In some embodiments, at least one ^RXc is -NHS (= O) (C _1-6 alkyl). In some embodiments, at least one ^R Xc, is -OC (= ^{O) R A1.} In some embodiments, at least one ^RXc is -OC (= O) (C _1-6 alkyl). In some embodiments, at least one ^RXc is -OC (= O) OR ^A1 . In some embodiments, at least one ^RXc is -OC (= O) O (C _1-6 alkyl). In some embodiments, at least one ^RXc is -OC (= O) N ( ^RA1 ) ₂ . In some embodiments, at least one ^RXc is -OC (= O) NH ( ^RA1 ). In some embodiments, at least one ^RXc is -OC (= O) N (C _1-6 alkyl) ₂ . In certain embodiments, at least one of ^{R Xc} is -C (= ^{O) R A1.} In some embodiments, at least one ^RXc is -C (= O) H. In some embodiments, at least one ^RXc is acetyl. In some embodiments, at least one ^RXc is -C (= O) (C _1-6 alkyl). In some embodiments, at least one ^RXc is -C (= O) OR ^A1 . In some embodiments, at least one ^RXc is -C (= O) OH. In some embodiments, at least one ^RXc is -C (= O) O (C _1-6 alkyl). In some embodiments, at least one ^RXc is -C (= O) N ( ^RA1 ) ₂ . In some embodiments, at least one ^RXc is -C (= O) NHR ^A1 . In some embodiments, at least one ^RXc is -C (= O) N (C _1-6 alkyl) ₂ . In some embodiments, at least one ^RXc is -C (= O) NH (C _1-6 alkyl). In some embodiments, at least one ^RXc is -C (= O) NH ₂ . In some embodiments, at least one ^{R Xc,} is -S (= ^{O) R A1.} In some embodiments, at least one ^RXc is -S (= O) (C _1-6 alkyl). In some embodiments, at least one ^RXc is -S (= O) N ( ^RA1 ) ₂ . In some embodiments, at least one ^RXc is -S (= O) NH ( ^RA1 ). In some embodiments, at least one ^RXc is -S (= O) NH ₂ . In some embodiments, at least one ^RXc is -S (= O) N (C _1-6 alkyl) ₂ . In some embodiments, at least one ^RXc is -S (= O) NH (C _1-6 alkyl). In some embodiments, at least one ^{R Xc,} is ^{_{-S (= O) 2 R A1}} . In some embodiments, at least one ^RXc is -S (= O) ₂ (C _1-6 alkyl). In some embodiments, at least one ^RXc is -S (= O) ₂ OR ^A1 . In some embodiments, at least one ^RXc is -S (= O) ₂ OH. In some embodiments, at least one ^RXc is -S (= O) ₂ N ( ^RA1 ) ₂ . In some embodiments, at least one ^RXc is -S (= O) ₂ NH ( ^RA1 ). In some embodiments, at least one ^RXc is -S (= O) ₂ NH ₂ . In some embodiments, at least one ^RXc is -S (= O) ₂ N (C _1-6 alkyl) ₂ . In some embodiments, at least one ^RXc is -S (= O) ₂ NH (C _1-6 alkyl).

のうちのいずれか一つである。
Ｒ^Ｄ１は、水素、ハロゲン、任意置換のアシル、任意置換のアルキル、任意置換のアルケニル、任意置換のアルキニル、任意置換のカルボシクリル、任意置換のヘテロシクリル、任意置換のアリール、任意置換のヘテロアリール、−ＣＮ、−ＮＯ_２、−ＯＲ^Ｄ１ａ、−Ｎ（Ｒ^Ｄ１ａ）_２、−ＳＲ^Ｄ１ａ、−ＣＨ_２ＯＲ^Ｄ１ａ、−ＣＨ_２Ｎ（Ｒ^Ｄ１ａ）_２、−ＣＨ_２ＳＲ^Ｄ１ａ、−Ｃ（＝Ｏ）Ｒ^Ｄ１ａ、−Ｃ（＝Ｏ）ＯＲ^Ｄ１ａ、−Ｃ（＝Ｏ）ＳＲ^Ｄ１ａ、−Ｃ（＝Ｏ）Ｎ（Ｒ^Ｄ１ａ）_２、−Ｃ（＝Ｓ）Ｒ^Ｄ１ａ、−Ｃ（＝Ｓ）ＯＲ^Ｄ１ａ、−Ｃ（＝Ｓ）ＳＲ^Ｄ１ａ、−Ｃ（＝Ｓ）Ｎ（Ｒ^Ｄ１ａ）_２、−Ｃ（＝ＮＲ^Ｄ１ａ）Ｒ^Ｄ１ａ、−Ｃ（＝ＮＲ^Ｄ１ａ）ＯＲ^Ｄ１ａ、−Ｃ（＝ＮＲ^Ｄ１ａ）ＳＲ^Ｄ１ａ、および−Ｃ（＝ＮＲ^Ｄ１ａ）Ｎ（Ｒ^Ｄ１ａ）_２からなる群より選択され、ここでＲ^Ｄ１ａの各々の出現は、独立して、水素、任意置換のアルキル、任意置換のアルケニル、任意置換のアルキニル、任意置換のカルボシクリル、任意置換のヘテロシクリル、任意置換のアリール、および任意置換のヘテロアリールからなる群より選択されるか、または２個のＲ^Ｄ１ａ基は、連結されて、任意に置換されたヘテロ環式環を形成し；
Ｒ^Ｄ２は、水素、ハロゲン、任意置換のアシル、任意置換のアルキル、任意置換のアルケニル、任意置換のアルキニル、任意置換のカルボシクリル、任意置換のヘテロシクリル、任意置換のアリール、任意置換のヘテロアリール、−ＣＮ、−ＮＯ_２、−ＯＲ^Ｄ２ａ、−Ｎ（Ｒ^Ｄ２ａ）_２、−ＳＲ^Ｄ２ａ、−ＣＨ_２ＯＲ^Ｄ２ａ、−ＣＨ_２Ｎ（Ｒ^Ｄ２ａ）_２、−ＣＨ_２ＳＲ^Ｄ２ａ、−Ｃ（＝Ｏ）Ｒ^Ｄ２ａ、−Ｃ（＝Ｏ）ＯＲ^Ｄ２ａ、−Ｃ（＝Ｏ）ＳＲ^Ｄ２ａ、−Ｃ（＝Ｏ）Ｎ（Ｒ^Ｄ２ａ）_２、−Ｃ（＝Ｓ）Ｒ^Ｄ２ａ、−Ｃ（＝Ｓ）ＯＲ^Ｄ２ａ、−Ｃ（＝Ｓ）ＳＲ^Ｄ２ａ、−Ｃ（＝Ｓ）Ｎ（Ｒ^Ｄ２ａ）_２、−Ｃ（＝ＮＲ^Ｄ２ａ）Ｒ^Ｄ２ａ、−Ｃ（＝ＮＲ^Ｄ２ａ）ＯＲ^Ｄ２ａ、−Ｃ（＝ＮＲ^Ｄ２ａ）ＳＲ^Ｄ２ａ、および−Ｃ（＝ＮＲ^Ｄ２ａ）Ｎ（Ｒ^Ｄ２ａ）_２からなる群より選択され、ここでＲ^Ｄ２ａの各々の出現は、独立して、水素、任意置換のアルキル、任意置換のアルケニル、任意置換のアルキニル、任意置換のカルボシクリル、任意置換のヘテロシクリル、任意置換のアリール、および任意置換のヘテロアリールからなる群より選択されるか、または２個のＲ^Ｄ２ａ基は、連結されて、任意に置換されたヘテロ環式環を形成し；
Ｒ^Ｄ３は、水素、ハロゲン、任意置換のアシル、任意置換のアルキル、任意置換のアルケニル、任意置換のアルキニル、任意置換のカルボシクリル、任意置換のヘテロシクリル、任意置換のアリール、任意置換のヘテロアリール、−ＣＮ、−ＮＯ_２、−ＯＲ^Ｄ３ａ、−Ｎ（Ｒ^Ｄ３ａ）_２、−ＳＲ^Ｄ３ａ、−ＣＨ_２ＯＲ^Ｄ３ａ、−ＣＨ_２Ｎ（Ｒ^Ｄ３ａ）_２、−ＣＨ_２ＳＲ^Ｄ３ａ、−Ｃ（＝Ｏ）Ｒ^Ｄ３ａ、−Ｃ（＝Ｏ）ＯＲ^Ｄ３ａ、−Ｃ（＝Ｏ）ＳＲ^Ｄ３ａ、−Ｃ（＝Ｏ）Ｎ（Ｒ^Ｄ３ａ）_２、−Ｃ（＝Ｓ）Ｒ^Ｄ３ａ、−Ｃ（＝Ｓ）ＯＲ^Ｄ３ａ、−Ｃ（＝Ｓ）ＳＲ^Ｄ３ａ、−Ｃ（＝Ｓ）Ｎ（Ｒ^Ｄ３ａ）_２、−Ｃ（＝ＮＲ^Ｄ３ａ）Ｒ^Ｄ３ａ、−Ｃ（＝ＮＲ^Ｄ３ａ）ＯＲ^Ｄ３ａ、−Ｃ（＝ＮＲ^Ｄ３ａ）ＳＲ^Ｄ３ａ、および−Ｃ（＝ＮＲ^Ｄ３ａ）Ｎ（Ｒ^Ｄ３ａ）_２からなる群より選択され、ここでＲ^Ｄ３ａの各々の出現は、独立して、水素、任意置換のアルキル、任意置換のアルケニル、任意置換のアルキニル、任意置換のカルボシクリル、任意置換のヘテロシクリル、任意置換のアリール、および任意置換のヘテロアリールからなる群より選択されるか、または２個のＲ^Ｄ３ａ基は、連結されて、任意に置換されたヘテロ環式環を形成し；
任意に、Ｒ^Ｄ１およびＲ^Ｄ３、またはＲ^Ｄ２およびＲ^Ｄ３、またはＲ^Ｄ１およびＲ^Ｄ２は、連結されて、任意に置換された炭素環式環または任意に置換されたヘテロ環式環を形成し；
Ｒ^Ｄ４は脱離基であり；
Ｒ^Ｄ５は、水素、Ｃ_１−６アルキル、または窒素保護基であり；
Ｙ^Ｚは、−Ｏ−、−Ｓ−、または−ＮＲ^Ｄ６−であって、ここでＲ^Ｄ６は、水素、Ｃ_１−６アルキル、または窒素保護基であり；
ａは、１または２であり；
ｚは、１、２、３、４、５または６であり；ならびに
任意に、Ｒ^Ｄ５および１個のＲ^Ｃは、連結されて、任意に置換されたヘテロ環式環を形成する。 In the compound of formula (A), ^RD is any electrophilic moiety attached to the pyridyl ring. In some embodiments, ^RD is expressed in formulas (i-1) to (i-18):

It is one of them.
^RD1 is hydrogen, halogen, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbometricyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl,- CN, -NO ₂ , -OR ^D1a , -N ( ^RD1a ) ₂ , -SR ^D1a , -CH ₂ OR ^D1a , -CH ₂ N ( ^RD1a ) ₂ , -CH ₂ SR ^D1a , -C (= O) R ^D1a , -C (= O) OR ^D1a , -C (= O) SR ^D1a , -C (= O) N ( ^RD1a ) ₂ , -C (= S) R ^D1a , -C (= S) OR ^D1a , -C (= S) SR ^D1a , -C (= S) N ( ^RD1a ) ₂ , -C (= NR ^D1a ) R ^D1a , -C (= NR ^D1a ) OR ^D1a , -C (= NR ^D1a) ) SR ^D1a , and -C (= NR ^D1a ) N ( ^RD1a ) ₂ selected from the group, where ^{each appearance of R D1a} is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl. , Arbitrarily substituted alkynyl, arbitrarily substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or two R ^D1a groups are linked and optionally Form a heterocyclic ring substituted with;
^RD2 is hydrogen, halogen, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbometricyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl,- CN, -NO ₂ , -OR ^D2a , -N ( ^RD2a ) ₂ , -SR ^D2a , -CH ₂ OR ^D2a , -CH ₂ N ( ^RD2a ) ₂ , -CH ₂ SR ^D2a , -C (= O) R ^D2a , -C (= O) OR ^D2a , -C (= O) SR ^D2a , -C (= O) N ( ^RD2a ) ₂ , -C (= S) R ^D2a , -C (= S) OR ^D2a , -C (= S) SR ^D2a , -C (= S) N ( ^RD2a ) ₂ , -C (= NR ^D2a ) R ^D2a , -C (= NR ^D2a ) OR ^D2a , -C (= NR ^D2a) ) SR ^D2a , and -C (= NR ^D2a ) N ( ^RD2a ) ₂ selected from the group, where ^{each appearance of R D2a} is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl. , Arbitrarily substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or two R ^D2a groups are linked and optionally Form a heterocyclic ring substituted with;
R ^D3 is hydrogen, halogen, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbometricyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl,- CN, -NO ₂ , -OR ^D3a , -N ( ^RD3a ) ₂ , -SR ^D3a , -CH ₂ OR ^D3a , -CH ₂ N ( ^RD3a ) ₂ , -CH ₂ SR ^D3a , -C (= O) R ^D3a , -C (= O) OR ^D3a , -C (= O) SR ^D3a , -C (= O) N ( ^RD3a ) ₂ , -C (= S) R ^D3a , -C (= S) OR ^D3a , -C (= S) SR ^D3a , -C (= S) N ( ^RD3a ) ₂ , -C (= NR ^D3a ) R ^D3a , -C (= NR ^D3a ) OR ^D3a , -C (= NR ^D3a) ) SR ^D3a , and -C (= NR ^D3a ) N ( ^RD3a ) ₂ selected from the group, where ^{each appearance of R D3a} is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl. , Arbitrarily substituted alkynyl, arbitrarily substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or two R ^D3a groups are linked and optionally Form a heterocyclic ring substituted with;
Optionally, ^RD1 and ^RD3 , or ^RD2 and ^RD3 , or ^RD1 and ^RD2 are linked to form an arbitrarily substituted carbocyclic ring or an arbitrarily substituted heterocyclic ring. ;
R ^D4 is a leaving group;
^RD5 is a hydrogen, C _1-6 alkyl, or nitrogen protecting group;
Y ^Z is -O-, -S-, or -NR ^D6- , where ^RD6 is a hydrogen, C _1-6 alkyl, or nitrogen protecting group;
a is 1 or 2;
z is 1, 2, 3, 4, 5 or 6; and optionally, R ^D5 and one ^RC are linked to form an arbitrarily substituted heterocyclic ring.

In some embodiments, the ^RD comprises a Michael acceptor portion. This Michael acceptor moiety may react with cysteine or other nucleophilic residues to allow covalent attachment of the compound to the target. In some embodiments, covalent bonds are irreversible. In other embodiments, the covalent bond is reversible. In some embodiments, ^RD is of formula (i-1). In some embodiments, ^RD is of formula (i-2). In some embodiments, the ^RD is of formula (i-3). In some embodiments, ^RD is of formula (i-4). In some embodiments, ^RD is of formula (i-5). In some embodiments, ^RD is of formula (i-6). In some embodiments, ^RD is of formula (i-7). In some embodiments, ^RD is of formula (i-8). In some embodiments, ^RD is of formula (i-9). In some embodiments, ^RD is of formula (i-10). In some embodiments, ^RD is of formula (i-11). In some embodiments, ^RD is of formula (i-12). In some embodiments, ^RD is of formula (i-13). In some embodiments, ^RD is of formula (i-14). In some embodiments, the ^RD is of formula (i-15). In some embodiments, the ^RD is of formula (i-16). In some embodiments, the ^RD is of formula (i-17).

In the compound of formula (A), ^RD may include the substituent ^RD1. In some embodiments, R ^D1 is H. In some embodiments, ^RD1 is a halogen. In some embodiments, R ^D1 is F. In some embodiments, ^RD1 is Cl. In some embodiments, R ^D1 is Br. In some embodiments, ^RD1 is I (iodine). In some embodiments, ^RD1 is a substituted acyl. In some embodiments, ^RD1 is an unsubstituted acyl. In some embodiments, ^RD1 is acetyl. In some embodiments, ^RD1 is a substituted alkyl. In some embodiments, ^RD1 is an unsubstituted alkyl. In some embodiments, ^RD1 is C _1-6 alkyl. In some embodiments, ^RD1 is methyl. In some embodiments, ^RD1 is ethyl. In some embodiments, ^RD1 is propyl. In some embodiments, ^RD1 is butyl. In some embodiments, ^RD1 is a substituted alkenyl. In some embodiments, ^RD1 is an unsubstituted alkenyl. In some embodiments, ^RD1 is a substituted alkynyl. In some embodiments, ^RD1 is an unsubstituted alkynyl. In some ^{embodiments, R D1} is a substituted carbocyclyl. In some ^{embodiments, R D1} is an unsubstituted carbocyclyl. In some embodiments, ^RD1 is a substituted heterocyclyl. In some embodiments, ^RD1 is an unsubstituted heterocyclyl. In some embodiments, ^RD1 is a substituted aryl. In some embodiments, ^RD1 is an unsubstituted aryl. In some embodiments, ^RD1 is a substituted phenyl. In some embodiments, ^RD1 is an unsubstituted phenyl. In some embodiments, ^RD1 is a substituted heteroaryl. In some embodiments, ^RD1 is an unsubstituted heteroaryl. In some embodiments, ^RD1 is a substituted pyridyl. In some embodiments, ^RD1 is an unsubstituted pyridyl. In some ^{embodiments, R D1} is -CN. In some ^{embodiments, R D1} is -NO _2. In some ^{embodiments, R} D1 ^{is -OR D1a.} In some ^{embodiments, R D1 is -N (R} _{D1a) 2.} In some embodiments, R ^D1 is -SR ^D1a . In some ^{embodiments, R D1} _is a -CH ^{2 OR D1a.} In some embodiments, ^RD1 is −CH ₂ N ( ^RD1a ) ₂ . In some embodiments, R ^D1 is -CH ₂ SR ^D1a .

In some embodiments, at least one R ^D1a is H. In some embodiments, at least one R ^D1a is a substituted acyl. In some embodiments, at least one R ^D1a is an unsubstituted acyl. In some embodiments, at least one ^RD1a is acetyl. In some embodiments, at least one ^RD1a is a substituted alkyl. In some embodiments, at least one ^RD1a is an unsubstituted alkyl. In some embodiments, at least one ^RD1a is C _1-6 alkyl. In some embodiments, at least one ^RD1a is methyl. In some embodiments, at least one ^RD1a is ethyl. In some embodiments, at least one ^RD1a is propyl. In some embodiments, at least one ^RD1a is butyl. In some embodiments, at least one ^RD1a is a substituted alkenyl. In some embodiments, at least one ^RD1a is an unsubstituted alkenyl. In some embodiments, at least one ^RD1a is a substituted alkynyl. In some embodiments, at least one ^RD1a is an unsubstituted alkynyl. In some embodiments, at least one R ^D1a is a substituted carbocyclyl. In some embodiments, at least one R ^D1a is an unsubstituted carbocyclyl. In some embodiments, at least one R ^D1a is a substituted heterocyclyl. In some embodiments, at least one ^RD1a is an unsubstituted heterocyclyl. In some embodiments, at least one R ^D1a is a substituted aryl. In some embodiments, at least one R ^D1a is an unsubstituted aryl. In some embodiments, at least one R ^D1a is a substituted phenyl. In some embodiments, at least one R ^D1a is an unsubstituted phenyl. In some embodiments, at least one R ^D1a is a substituted heteroaryl. In some embodiments, at least one R ^D1a is an unsubstituted heteroaryl. In some embodiments, at least one R ^D1a is a substituted pyridyl. In some embodiments, at least one ^RD1a is an unsubstituted pyridyl. In some embodiments, at least one ^RD1a is a nitrogen protecting group if it is attached to a nitrogen atom. In some embodiments, at least one ^RD1a is Bn, BOC, Cbz, Fmoc, trifluoroacetyl, triphenylmethyl or Ts when attached to a nitrogen atom. In some embodiments, R ^D1a is an oxygen protecting group when attached to an oxygen atom. In some embodiments, ^RD1a is silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl or benzoyl when attached to an oxygen atom. In some embodiments, R ^D1a is a sulfur protecting group when attached to a sulfur atom. In some embodiments, ^RD1a is acetamidemethyl, t-Bu, 3-nitro-2-pyridinesulfenyl, 2-pyridine-sulphenyl or triphenylmethyl when attached to a sulfur atom. In some embodiments, the two R ^D1a groups are linked to form a substituted heterocyclic ring. In some embodiments, the two R ^D1a groups are linked to form an unsubstituted heterocyclic ring.

In the compound of formula (A), ^RD may include the substituent ^RD2. In some embodiments, R ^D2 is H. In some embodiments, ^RD2 is a halogen. In some embodiments, R ^D2 is F. In some embodiments, ^RD2 is Cl. In some embodiments, R ^D2 is Br. In some embodiments, ^RD2 is I (iodine). In some embodiments, ^RD2 is a substituted acyl. In some embodiments, ^RD2 is an unsubstituted acyl. In some embodiments, ^RD2 is acetyl. In some embodiments, ^RD2 is a substituted alkyl. In some embodiments, ^RD2 is an unsubstituted alkyl. In some embodiments, ^RD2 is a C _1-6 alkyl. In some embodiments, ^RD2 is methyl. In some embodiments, ^RD2 is ethyl. In some embodiments, ^RD2 is propyl. In some embodiments, ^RD2 is butyl. In some embodiments, ^RD2 is a substituted alkenyl. In some embodiments, ^RD2 is an unsubstituted alkenyl. In some embodiments, ^RD2 is a substituted alkynyl. In some embodiments, ^RD2 is an unsubstituted alkynyl. In some ^{embodiments, R D2} is substituted carbocyclyl. In some ^{embodiments, R D2} is an unsubstituted carbocyclyl. In some embodiments, ^RD2 is a substituted heterocyclyl. In some embodiments, ^RD2 is an unsubstituted heterocyclyl. In some embodiments, ^RD2 is a substituted aryl. In some embodiments, ^RD2 is an unsubstituted aryl. In some embodiments, ^RD2 is a substituted phenyl. In some embodiments, ^RD2 is an unsubstituted phenyl. In some embodiments, ^RD2 is a substituted heteroaryl. In some embodiments, ^RD2 is an unsubstituted heteroaryl. In some embodiments, ^RD2 is a substituted pyridyl. In some embodiments, ^RD2 is an unsubstituted pyridyl. In some ^{embodiments, R D2} is -CN. In some ^{embodiments, R D2} is -NO _2. In some embodiments, R ^D2 is −OR ^D2a . In some ^{embodiments, R D2 is -N (R} _{D2a) 2.} In some embodiments, R ^D2 is -SR ^D2a . In some ^{embodiments, R D2} _is -CH ^{2 OR D2a.} In some embodiments, the ^RD2 is −CH ₂ N ( ^RD2a ) ₂ . In some embodiments, the R ^D2 is -CH ₂ SR ^D2a .

In some embodiments, at least one R ^D2a is H. In some embodiments, at least one R ^D2a is a substituted acyl. In some embodiments, at least one R ^D2a is an unsubstituted acyl. In some embodiments, at least one ^RD2a is acetyl. In some embodiments, at least one ^RD2a is a substituted alkyl. In some embodiments, at least one ^RD2a is an unsubstituted alkyl. In some embodiments, at least one ^RD2a is C _1-6 alkyl. In some embodiments, at least one ^RD2a is methyl. In some embodiments, at least one ^RD2a is ethyl. In some embodiments, at least one ^RD2a is propyl. In some embodiments, at least one ^RD2a is butyl. In some embodiments, at least one ^RD2a is a substituted alkenyl. In some embodiments, at least one ^RD2a is an unsubstituted alkenyl. In some embodiments, at least one ^RD2a is a substituted alkynyl. In some embodiments, at least one ^RD2a is an unsubstituted alkynyl. In some embodiments, at least one R ^D2a is a substituted carbocyclyl. In some embodiments, at least one R ^D2a is an unsubstituted carbocyclyl. In some embodiments, at least one R ^D2a is a substituted heterocyclyl. In some embodiments, at least one ^RD2a is an unsubstituted heterocyclyl. In some embodiments, at least one R ^D2a is a substituted aryl. In some embodiments, at least one R ^D2a is an unsubstituted aryl. In some embodiments, at least one R ^D2a is a substituted phenyl. In some embodiments, at least one R ^D2a is an unsubstituted phenyl. In some embodiments, at least one ^RD2a is a substituted heteroaryl. In some embodiments, at least one ^RD2a is an unsubstituted heteroaryl. In some embodiments, at least one R ^D2a is a substituted pyridyl. In some embodiments, at least one ^RD2a is an unsubstituted pyridyl. In some embodiments, at least one ^RD2a is a nitrogen protecting group if it is attached to a nitrogen atom. In some embodiments, at least one ^RD2a is Bn, BOC, Cbz, Fmoc, trifluoroacetyl, triphenylmethyl or Ts when attached to a nitrogen atom. In some embodiments, R ^D2a is an oxygen protecting group when attached to an oxygen atom. In some embodiments, ^RD2a is silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl or benzoyl when attached to an oxygen atom. In some embodiments, R ^D2a is a sulfur protecting group when attached to a sulfur atom. In some embodiments, ^RD2a is acetamidemethyl, t-Bu, 3-nitro-2-pyridinesulfenyl, 2-pyridine-sulphenyl or triphenylmethyl when attached to a sulfur atom. In some embodiments, the two R ^D2a groups are linked to form a substituted heterocyclic ring. In some embodiments, the two R ^D2a groups are linked to form an unsubstituted heterocyclic ring.

In the compound of formula (A), ^RD may include substituent ^RD3. In some embodiments, R ^D3 is H. In some embodiments, ^RD3 is a halogen. In some embodiments, R ^D3 is F. In some embodiments, ^RD3 is Cl. In some embodiments, R ^D3 is Br. In some embodiments, ^RD3 is I (iodine). In some embodiments, ^RD3 is a substituted acyl. In some embodiments, ^RD3 is an unsubstituted acyl. In some embodiments, ^RD3 is acetyl. In some embodiments, ^RD3 is a substituted alkyl. In some embodiments, ^RD3 is an unsubstituted alkyl. In some embodiments, ^RD3 is a C _1-6 alkyl. In some embodiments, ^RD3 is methyl. In some embodiments, ^RD3 is ethyl. In some embodiments, ^RD3 is propyl. In some embodiments, ^RD3 is butyl. In some embodiments, ^RD3 is a substituted alkenyl. In some embodiments, ^RD3 is an unsubstituted alkenyl. In some embodiments, ^RD3 is a substituted alkynyl. In some embodiments, ^RD3 is an unsubstituted alkynyl. In some ^{embodiments, R D3} is substituted carbocyclyl. In some embodiments, ^RD3 is an unsubstituted carbocyclyl. In some embodiments, ^RD3 is a substituted heterocyclyl. In some embodiments, ^RD3 is an unsubstituted heterocyclyl. In some embodiments, ^RD3 is a substituted aryl. In some embodiments, ^RD3 is an unsubstituted aryl. In some embodiments, ^RD3 is a substituted phenyl. In some embodiments, ^RD3 is an unsubstituted phenyl. In some embodiments, ^RD3 is a substituted heteroaryl. In some embodiments, ^RD3 is an unsubstituted heteroaryl. In some embodiments, ^RD3 is a substituted pyridyl. In some embodiments, ^RD3 is an unsubstituted pyridyl. In some ^{embodiments, R D3} is -CN. In some embodiments, R ^D3 is -NO ₂ . In some embodiments, R ^D3 is -OR ^D3a . In some ^{embodiments, R D3 is -N (R} _{D3a) 2.} In some embodiments, R ^D3 is -SR ^D3a . In some ^{embodiments, R D3} _is -CH ^{2 OR D3a.} In some embodiments, the R ^D3 is −CH ₂ N ( ^RD3a ) ₂ . In some embodiments, the R ^D3 is -CH ₂ SR ^D3a .

In some embodiments, at least one R ^D3a is H. In some embodiments, at least one ^RD3a is a substituted acyl. In some embodiments, at least one ^RD3a is an unsubstituted acyl. In some embodiments, at least one ^RD3a is acetyl. In some embodiments, at least one ^RD3a is a substituted alkyl. In some embodiments, at least one ^RD3a is an unsubstituted alkyl. In some embodiments, at least one ^RD3a is C _1-6 alkyl. In some embodiments, at least one ^RD3a is methyl. In some embodiments, at least one ^RD3a is ethyl. In some embodiments, at least one ^RD3a is propyl. In some embodiments, at least one ^RD3a is butyl. In some embodiments, at least one ^RD3a is a substituted alkenyl. In some embodiments, at least one ^RD3a is an unsubstituted alkenyl. In some embodiments, at least one ^RD3a is a substituted alkynyl. In some embodiments, at least one ^RD3a is an unsubstituted alkynyl. In some embodiments, at least one R ^D3a is a substituted carbocyclyl. In some embodiments, at least one ^RD3a is an unsubstituted carbocyclyl. In some embodiments, at least one ^RD3a is a substituted heterocyclyl. In some embodiments, at least one ^RD3a is an unsubstituted heterocyclyl. In some embodiments, at least one ^RD3a is a substituted aryl. In some embodiments, at least one ^RD3a is an unsubstituted aryl. In some embodiments, at least one ^RD3a is a substituted phenyl. In some embodiments, at least one ^RD3a is an unsubstituted phenyl. In some embodiments, at least one ^RD3a is a substituted heteroaryl. In some embodiments, at least one ^RD3a is an unsubstituted heteroaryl. In some embodiments, at least one ^RD3a is a substituted pyridyl. In some embodiments, at least one ^RD3a is an unsubstituted pyridyl. In some embodiments, at least one ^RD3a is a nitrogen protecting group if it is attached to a nitrogen atom. In some embodiments, at least one ^RD3a is Bn, BOC, Cbz, Fmoc, trifluoroacetyl, triphenylmethyl or Ts when attached to a nitrogen atom. In some embodiments, R ^D3a is an oxygen protecting group when attached to an oxygen atom. In some embodiments, ^RD3a is silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl or benzoyl when attached to an oxygen atom. In some embodiments, ^RD3a is a sulfur protecting group when attached to a sulfur atom. In some embodiments, ^RD3a is acetamidemethyl, t-Bu, 3-nitro-2-pyridinesulfenyl, 2-pyridine-sulphenyl or triphenylmethyl when attached to a sulfur atom. In some embodiments, the two R ^D3a groups are linked to form a substituted heterocyclic ring. In some embodiments, the two R ^D3a groups are linked to form an unsubstituted heterocyclic ring.

In the compound of formula (A), ^RD may include the substituent ^RD4. In some embodiments, ^RD4 is a leaving group. In some embodiments, ^RD4 is a halogen. In some embodiments, R ^D4 is F. In some embodiments, ^RD4 is Cl. In some embodiments, R ^D4 is Br. In some embodiments, ^RD4 is I (iodine). In some embodiments, R ^D4 is -OS (= O) _w R ^D4a . In some embodiments, w is 1. In some embodiments, w is 2. In some ^{embodiments, R D4} is -OMs. In some ^{embodiments, R D4} is -OTf. In some ^{embodiments, R D4} is -OTs. In some ^{embodiments, R D4} is -OBs. In some embodiments, ^RD4 is 2-nitrobenzenesulfonyloxy. In some embodiments, R ^D4 is -OR ^D4a . In some ^{embodiments, R D4} is -OMe. In some embodiments, R ^D4 is -OCF ₃ . In some ^{embodiments, R D4} is -OPh. In some embodiments, R ^D4 is -OC (= O) R ^D4a . In some ^{embodiments, R} D4 is -OC (= O) Me. In some ^{embodiments, R} D4 is -OC (= O) CF _3. In some ^{embodiments, R} D4 is -OC (= O) Ph. In some ^{embodiments, R} D4 is -OC (= O) Cl. In some ^{embodiments, R} D4 is -OC (= ^{O) OR D4a.} In some ^{embodiments, R} D4 is -OC (= O) OMe. In some ^{embodiments, R} D4 is -OC (= O) O (t -Bu).

In some embodiments, ^RD4a is a substituted alkyl. In some embodiments, ^RD4a is an unsubstituted alkyl. In some embodiments, R ^D4a is a C _1-6 alkyl. In some embodiments, ^RD4a is methyl. In some embodiments, ^RD4a is ethyl. In some embodiments, ^RD4a is propyl. In some embodiments, ^RD4a is butyl. In some embodiments, ^RD4a is a substituted alkenyl. In some embodiments, ^RD4a is an unsubstituted alkenyl. In some embodiments, ^RD4a is vinyl. In some embodiments, ^RD4a is a substituted alkynyl. In some embodiments, ^RD4a is an unsubstituted alkynyl. In some embodiments, ^RD4a is ethynyl. In some embodiments, ^RD4a is a substituted carbocyclyl. In some embodiments, ^RD4a is an unsubstituted carbocyclyl. In some embodiments, ^RD4a is a substituted heterocyclyl. In some embodiments, ^RD4a is an unsubstituted heterocyclyl. In some embodiments, ^RD4a is a substituted aryl. In some embodiments, ^RD4a is an unsubstituted aryl. In some embodiments, ^RD4a is a substituted phenyl. In some embodiments, ^RD4a is an unsubstituted phenyl. In some embodiments, ^RD4a is a substituted heteroaryl. In some embodiments, ^RD4a is an unsubstituted heteroaryl. In some embodiments, ^RD4a is a substituted pyridyl. In some embodiments, ^RD4a is an unsubstituted pyridyl.

In the compound of formula (A), ^RD may include substituent ^RD5. In some embodiments, ^RD5 is H. In some embodiments, ^RD5 is a substituted alkyl. In some embodiments, ^RD5 is an unsubstituted alkyl. In some embodiments, ^RD5 is a C _1-6 alkyl. In some embodiments, ^RD5 is methyl. In some embodiments, ^RD5 is ethyl. In some embodiments, ^RD5 is propyl. In some embodiments, ^RD5 is butyl. In some embodiments, ^RD5 is a nitrogen protecting group. In some embodiments, the ^RD5 is Bn, BOC, Cbz, Fmoc, trifluoroacetyl, triphenylmethyl or Ts.

In some embodiments, R ^D1 and R ^D2 are each hydrogen. In some embodiments, R ^D1 and R ^D3 are each hydrogen. In some embodiments, R ^D2 and R ^D3 are each hydrogen. In some embodiments, ^RD1 , ^RD2 , and ^RD3 are each hydrogen. In some embodiments, ^RD1 , ^RD2 , and ^RD3 , and ^RD5 are each hydrogen.

In some embodiments, a is 1. In some embodiments, a is 2.

In some embodiments, z is zero. In some embodiments, z is 1. In some embodiments, z is 2. In some embodiments, z is 3. In some embodiments, z is 4. In some embodiments, z is 5. In some embodiments, z is 6.

In some embodiments, Y is −O−. In some embodiments, Y is −C (= O) −. In some embodiments, Y is −S−. In some embodiments, Y is −C (= S) −. In some embodiments, Y is −NR ^D6- , where ^RD6 is a hydrogen, C _1-6 alkyl, or nitrogen protecting group. In some embodiments, Y is -NH-. In some embodiments, Y is -NCH _3- . In some embodiments, Y is −N (BOC) −. In some embodiments, Y is -N (Fmoc)-. In some embodiments, Y is −N (Cbz) −. In some embodiments, Y is −N (Bn) −. In some embodiments, Y is −C (= NR ^D6 ) −, where ^RD6 is a hydrogen, C _1-6 alkyl, or nitrogen protecting group. In some embodiments, Y is −C (= NH) −. In some embodiments, Y is −C (= NCH ₃ ) −. In some embodiments, Y is −C (= NTs) −. In some embodiments, Y is −C (= NBn) −. In some embodiments, Y is −C (= NCH (Ph) ₂ ) −.

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belongs to.

Various combinations of certain aspects of formula (A) are further contemplated herein.

の化合物であって、式中、Ｒ^Ｘ、Ｒ^Ａ、Ｒ^Ｂおよびｌは、本明細書において定義される。ある態様において、Ｒ^Ａは、置換または未置換Ｃ_１−６アルキルである。ある態様において、Ｒ^Ａは、メチルである。ある態様において、ｌは、１である。ある態様において、ｌは１であり；Ｒ^Ｂは、アミドリンカーの結合点に対してメタ位にある。ある態様において、ｌは、２である。ある態様において、ｌは２であり；２個のＲ^Ｂ基は、アミドリンカーの結合点に対してメタ位にある。ある態様において、ｌは２であり；１個のＲ^Ｂ基は、アミドリンカーの結合点に対してメタであり；第２のＲ^Ｂ基は、アミドリンカーの結合点に対してパラ位にある。ある態様において、１個のＲ^Ｂ基は、置換または未置換Ｃ_１−６アルキルである。ある態様において、１個のＲ^Ｂ基は、１個の−ＣＮ基で置換されたＣ_１−６アルキルである。ある態様において、１個のＲ^Ｂ基は、

である。ある態様において、１個のＲ^Ｂ基は、置換または未置換−ＣＨ_２−（ピペラジニル）である。ある態様において、１個のＲ^Ｂ基は、

であって、ここで、アルキルは、任意に置換されている。ある態様において、１個のＲ^Ｂ基は、

であって、ここで、アルキルは、未置換である。ある態様において、１個のＲ^Ｂ基は、

である。ある態様において、１個のＲ^Ｂ基は、ハロアルキルである。ある態様において、１個のＲ^Ｂ基は、−ＣＦ_３である。ある態様において、１個のＲ^Ｂ基は、置換または未置換イミダゾリルである。ある態様において、１個のＲ^Ｂ基は、

であって、ここで、アルキルは、任意に置換されている。ある態様において、１個のＲ^Ｂ基は、

であって、ここで、アルキルは、未置換である。ある態様において、１個のＲ^Ｂ基は、

である。ある態様において、１個のＲ^Ｂ基は、置換または未置換ピペラジニルである。ある態様において、１個のＲ^Ｂ基は、

であって、ここで、アルキルは、任意に置換されている。ある態様において、１個のＲ^Ｂ基は、

であって、ここで、アルキルは、未置換である。ある態様において、１個のＲ^Ｂ基は、

である。ある態様において、１個のＲ^Ｂ基は、置換または未置換モルホリンである。ある態様において、２個のＲ^Ｂ基は、置換または未置換モルホリンである。ある態様において、Ｒ^Ｘは−Ｎ（Ｒ^Ａ１）Ｎ（Ｒ^Ａ１）_２である。ある態様において、Ｒ^Ｘは−Ｎ（Ｒ^Ａ１）Ｎ（Ｒ^Ａ１）_２；およびＲ^Ａの各々の場合は、水素、メチルまたはアセチルである。ある態様において、Ｒ^Ｘは−ＮＨＮＭｅ_２または−ＮＨＮＨＡｃである。ある態様において、Ｒ^ＸはＮＨ_２である。ある態様において、Ｒ^Ｘは−ＮＨ（Ｒ^Ａ１）である。ある態様において、Ｒ^Ｘは−ＮＨ（Ｒ^Ａ１）；およびＲ^Ａ１は置換または未置換のＣ_１−６アルキルである。ある態様において、Ｒ^Ｘは−ＮＨ（Ｒ^Ａ１）；およびＲ^Ａ１は置換または未置換のメチルである。ある態様において、Ｒ^Ｘは-ＮＨ（Ｒ^Ａ１）；およびＲ^Ａ１はアシルである。ある態様において、Ｒ^Ｘは−ＮＨ（Ｒ^Ａ１）；およびＲ^Ａ１は置換または未置換の−Ｃ（＝Ｏ）−（Ｃ_１−６アルキル）である。ある態様において、Ｒ^Ｘは−ＮＨ（Ｒ^Ａ１）；およびＲ^Ａ１はアセチルまたはプロピオニルである。ある態様において、Ｒ^Ｘは−ＮＨ（Ｒ^Ａ１）；およびＲ^Ａ１は置換または未置換の−Ｃ（＝Ｏ）−（カルボシクリル）である。ある態様において、Ｒ^Ｘは−ＮＨ（Ｒ^Ａ１）；およびＲ^Ａ１は置換または未置換の−Ｃ（＝Ｏ）−（シクロプロピル）である。ある態様において、Ｒ^Ｘは−ＮＨ（Ｒ^Ａ１）；およびＲ^Ａ１は置換または未置換のヘテロアリールである。ある態様において、Ｒ^Ｘは−ＮＨ（Ｒ^Ａ１）；およびＲ^Ａ１は置換または未置換のピラゾールである。ある態様において、Ｒ^Ｘは−ＮＨ（Ｒ^Ａ１）；およびＲ^Ａ１は置換または未置換のイソキサゾールである。ある態様において、Ｒ^Ｘは−ＮＨ（Ｒ^Ａ１）；およびＲ^Ａ１は置換または未置換のピリミジンである。ある態様において、Ｒ^Ｘは−ＮＨ（Ｒ^Ａ１）；およびＲ^Ａ１は置換または未置換のヘテロシクリルである。ある態様において、Ｒ^Ｘは−ＮＨ（Ｒ^Ａ１）；およびＲ^Ａ１は置換または未置換のアゼチジンである。ある態様において、Ｒ^Ｘは−ＮＨ（Ｒ^Ａ１）；およびＲ^Ａ１は置換または未置換のオキセタンである。 For example, in some embodiments, the compounds of formula (A) are of formula (A1) or (A2) :.

A compound ^{wherein, R X, R A, R} B and l are as defined herein. In some embodiments, ^RA is a substituted or unsubstituted C _1-6 alkyl. In some embodiments, ^RA is methyl. In some embodiments, l is 1. In some embodiments, l is an 1; R ^B is meta to the point of attachment of the amide linker. In some embodiments, l is 2. In some embodiments, l is 2; two R ^B groups are in the meta position relative to the point of attachment of the amide linker. In some embodiments, l is 2; one R ^B groups is an meta to the point of attachment of the amide linker; second R ^B groups are in the para position relative to the point of attachment of the amide linker .. In certain embodiments, one ^{R B} groups are substituted or unsubstituted _{C 1-6} alkyl. In certain embodiments, one ^{R B} groups are _{C 1-6} alkyl substituted with one -CN group. In certain embodiments, one ^{R B} group,

Is. In certain embodiments, one ^{R B} group, a substituted or unsubstituted -CH ₂ - is (piperazinyl). In certain embodiments, one ^{R B} group,

And here, the alkyl is optionally substituted. In certain embodiments, one ^{R B} group,

And here, the alkyl is unsubstituted. In certain embodiments, one ^{R B} group,

Is. In certain embodiments, one R ^B groups are haloalkyl. In certain embodiments, one ^{R B} groups are -CF _3. In certain embodiments, one R ^B groups are substituted or unsubstituted imidazolyl. In certain embodiments, one ^{R B} group,

And here, the alkyl is optionally substituted. In certain embodiments, one ^{R B} group,

And here, the alkyl is unsubstituted. In certain embodiments, one ^{R B} group,

Is. In certain embodiments, one R ^B groups are substituted or unsubstituted piperazinyl. In certain embodiments, one ^{R B} group,

And here, the alkyl is optionally substituted. In certain embodiments, one ^{R B} group,

And here, the alkyl is unsubstituted. In certain embodiments, one ^{R B} group,

Is. In certain embodiments, one R ^B groups are substituted or unsubstituted morpholine. In some embodiments, two R ^B groups are substituted or unsubstituted morpholine. In some embodiments, ^{R X} is ^{-N (R A1) N (R} A1) 2. In some embodiments, ^{R X} is ^{-N (R A1) N (R} A1) 2; in the case of each and ^{R A,} hydrogen, methyl or acetyl. In some embodiments, ^{R X} is -NHNMe ₂ or -NHNHAc. In some embodiments, ^{R X} is NH _2. In some embodiments, ^{R X} is -NH ^{(R A1).} In some embodiments, ^{R X} is -NH ^{(R A1);} and ^{R A1} is _{C 1-6} alkyl substituted or unsubstituted. In some embodiments, ^{R X} is -NH ^{(R A1);} a and ^{R A1} represents a substituted or unsubstituted methyl. In some embodiments, ^{R X} is -NH ^{(R A1);} and ^{R A1} is acyl. In some embodiments, ^{R X} is -NH ^{(R A1);} and ^{R A1} represents a substituted or unsubstituted -C (= O) - is a _{(C 1-6} alkyl). In some embodiments, ^{R X} is -NH ^{(R A1);} and ^{R A1} is acetyl or propionyl. In some embodiments, ^{R X} is -NH ^{(R A1);} and ^{R A1} represents a substituted or unsubstituted -C (= O) - is a (carbocyclyl). In some embodiments, ^{R X} is -NH ^{(R A1);} and ^{R A1} represents a substituted or unsubstituted -C (= O) - is (cyclopropyl). In some embodiments, ^{R X} is -NH ^{(R A1);} a and ^{R A1} represents a substituted or unsubstituted heteroaryl. In some embodiments, ^{R X} is -NH ^{(R A1);} and ^{R A1} is pyrazole substituted or unsubstituted. In some embodiments, ^{R X} is -NH ^{(R A1);} the and ^{R A1} is isoxazole substituted or unsubstituted. In some embodiments, ^{R X} is -NH ^{(R A1);} a and ^{R A1} represents a substituted or unsubstituted pyrimidine. In some embodiments, ^{R X} is -NH ^{(R A1);} a and ^{R A1} represents a substituted or unsubstituted heterocyclyl. In some embodiments, ^{R X} is -NH ^{(R A1);} a and ^{R A1} azetidine substituted or unsubstituted. In some embodiments, ^{R X} is -NH ^{(R A1);} a and ^{R A1} represents a substituted or unsubstituted oxetane.

の化合物であって、式中、Ｒ^Ｘａ、Ｒ^Ｘｃ、Ｒ^Ａ、Ｒ^Ｂおよびｌは、本明細書において定義される。ある態様において、Ｒ^Ａは、置換または未置換Ｃ_１−６アルキルである。ある態様において、Ｒ^Ａは、メチルである。ある態様において、ｌは、１である。ある態様において、ｌは１であり；Ｒ^Ｂは、アミドリンカーの結合点に対してメタ位にある。ある態様において、ｌは、２である。ある態様において、ｌは２であり；２個のＲ^Ｂ基は、アミドリンカーの結合点に対してメタ位にある。ある態様において、ｌは２であり；１個のＲ^Ｂ基は、アミドリンカーの結合点に対してメタであり；第２のＲ^Ｂ基は、アミドリンカーの結合点に対してパラ位にある。ある態様において、１個のＲ^Ｂ基は、置換または未置換Ｃ_１−６アルキルである。ある態様において、１個のＲ^Ｂ基は、１個の−ＣＮ基で置換されたＣ_１−６アルキルである。ある態様において、１個のＲ^Ｂ基は、

である。ある態様において、１個のＲ^Ｂ基は、置換または未置換−ＣＨ_２−（ピペラジニル）である。ある態様において、１個のＲ^Ｂ基は、

であって、ここで、アルキルは、任意に置換されている。ある態様において、１個のＲ^Ｂ基は、

であって、ここで、アルキルは、未置換である。ある態様において、１個のＲ^Ｂ基は、

である。ある態様において、１個のＲ^Ｂ基は、ハロアルキルである。ある態様において、１個のＲ^Ｂ基は、−ＣＦ_３である。ある態様において、１個のＲ^Ｂ基は、置換または未置換イミダゾリルである。ある態様において、１個のＲ^Ｂ基は、

であって、ここで、アルキルは、任意に置換されている。ある態様において、１個のＲ^Ｂ基は、

であって、ここで、アルキルは、未置換である。ある態様において、１個のＲ^Ｂ基は、

である。ある態様において、１個のＲ^Ｂ基は、置換または未置換ピペラジニルである。ある態様において、１個のＲ^Ｂ基は、

であって、ここで、アルキルは、任意に置換されている。ある態様において、１個のＲ^Ｂ基は、

であって、ここで、アルキルは、未置換である。ある態様において、１個のＲ^Ｂ基は、

である。ある態様において、１個のＲ^Ｂ基は、置換または未置換モルホリンである。ある態様において、２個のＲ^Ｂ基は、置換または未置換モルホリンである。ある態様において、Ｒ^Ｘｃの全ての場合は、水素である。ある態様において、Ｒ^Ｘａは、置換または未置換Ｃ_１−６アルキルである。ある態様において、Ｒ^Ｘａは、メチルまたはエチルである。 In some embodiments, the compounds of formula (A1) are of formula (A1-a), (A1-b), (A1-c) or (A1-d) :.

A compound ^{wherein, R Xa, R Xc, R} A, R B and l are as defined herein. In some embodiments, ^RA is a substituted or unsubstituted C _1-6 alkyl. In some embodiments, ^RA is methyl. In some embodiments, l is 1. In some embodiments, l is an 1; R ^B is meta to the point of attachment of the amide linker. In some embodiments, l is 2. In some embodiments, l is 2; two R ^B groups are in the meta position relative to the point of attachment of the amide linker. In some embodiments, l is 2; one R ^B groups is an meta to the point of attachment of the amide linker; second R ^B groups are in the para position relative to the point of attachment of the amide linker .. In certain embodiments, one ^{R B} groups are substituted or unsubstituted _{C 1-6} alkyl. In certain embodiments, one ^{R B} groups are _{C 1-6} alkyl substituted with one -CN group. In certain embodiments, one ^{R B} group,

Is. In certain embodiments, one ^{R B} group, a substituted or unsubstituted -CH ₂ - is (piperazinyl). In certain embodiments, one ^{R B} group,

And here, the alkyl is optionally substituted. In certain embodiments, one ^{R B} group,

And here, the alkyl is unsubstituted. In certain embodiments, one ^{R B} group,

Is. In certain embodiments, one R ^B groups are haloalkyl. In certain embodiments, one ^{R B} groups are -CF _3. In certain embodiments, one R ^B groups are substituted or unsubstituted imidazolyl. In certain embodiments, one ^{R B} group,

And here, the alkyl is optionally substituted. In certain embodiments, one ^{R B} group,

And here, the alkyl is unsubstituted. In certain embodiments, one ^{R B} group,

Is. In certain embodiments, one R ^B groups are substituted or unsubstituted piperazinyl. In certain embodiments, one ^{R B} group,

And here, the alkyl is optionally substituted. In certain embodiments, one ^{R B} group,

And here, the alkyl is unsubstituted. In certain embodiments, one ^{R B} group,

Is. In certain embodiments, one R ^B groups are substituted or unsubstituted morpholine. In some embodiments, two R ^B groups are substituted or unsubstituted morpholine. In some embodiments, all cases of ^{RXc are hydrogen.} In some embodiments, ^RXa is a substituted or unsubstituted C _1-6 alkyl. In some embodiments, ^RXa is methyl or ethyl.

の化合物であって、式中、Ｒ^Ｘａ、Ｒ^Ｘｃ、Ｒ^Ａ、Ｒ^Ｂおよびｌは、本明細書において定義される。ある態様において、Ｒ^Ａは、置換または未置換Ｃ_１−６アルキルである。ある態様において、Ｒ^Ａは、メチルである。ある態様において、ｌは、１である。ある態様において、ｌは１であり；Ｒ^Ｂは、アミドリンカーの結合点に対してメタ位にある。ある態様において、ｌは、２である。ある態様において、ｌは２であり；２個のＲ^Ｂ基は、アミドリンカーの結合点に対してメタ位にある。ある態様において、ｌは２であり；１個のＲ^Ｂ基は、アミドリンカーの結合点に対してメタであり；第２のＲ^Ｂ基は、アミドリンカーの結合点に対してパラ位にある。ある態様において、１個のＲ^Ｂ基は、置換または未置換Ｃ_１−６アルキルである。ある態様において、１個のＲ^Ｂ基は、１個の−ＣＮ基で置換されたＣ_１−６アルキルである。ある態様において、１個のＲ^Ｂ基は、

である。ある態様において、１個のＲ^Ｂ基は、置換または未置換−ＣＨ_２−（ピペラジニル）である。ある態様において、１個のＲ^Ｂ基は、

であって、ここで、アルキルは、任意に置換されている。ある態様において、１個のＲ^Ｂ基は、

であって、ここで、アルキルは、未置換である。ある態様において、１個のＲ^Ｂ基は、

である。ある態様において、１個のＲ^Ｂ基は、ハロアルキルである。ある態様において、１個のＲ^Ｂ基は、−ＣＦ_３である。ある態様において、１個のＲ^Ｂ基は、置換または未置換イミダゾリルである。ある態様において、１個のＲ^Ｂ基は、

であって、ここで、アルキルは、任意に置換されている。ある態様において、１個のＲ^Ｂ基は、

であって、ここで、アルキルは、未置換である。ある態様において、１個のＲ^Ｂ基は、

である。ある態様において、１個のＲ^Ｂ基は、置換または未置換ピペラジニルである。ある態様において、１個のＲ^Ｂ基は、

であって、ここで、アルキルは、任意に置換されている。ある態様において、１個のＲ^Ｂ基は、

であって、ここで、アルキルは、未置換である。ある態様において、１個のＲ^Ｂ基は、

である。ある態様において、１個のＲ^Ｂ基は、置換または未置換モルホリンである。ある態様において、２個のＲ^Ｂ基は、置換または未置換モルホリンである。ある態様において、Ｒ^Ｘｃの全ての場合は、水素である。ある態様において、Ｒ^Ｘａは、置換または未置換Ｃ_１−６アルキルである。ある態様において、Ｒ^Ｘａは、メチルまたはエチルである。 In some embodiments, the compounds of formula (A2) are of formula (A2-a), (A2-b), (A2-c) or (A2-d):

A compound ^{wherein, R Xa, R Xc, R} A, R B and l are as defined herein. In some embodiments, ^RA is a substituted or unsubstituted C _1-6 alkyl. In some embodiments, ^RA is methyl. In some embodiments, l is 1. In some embodiments, l is an 1; R ^B is meta to the point of attachment of the amide linker. In some embodiments, l is 2. In some embodiments, l is 2; two R ^B groups are in the meta position relative to the point of attachment of the amide linker. In some embodiments, l is 2; one R ^B groups is an meta to the point of attachment of the amide linker; second R ^B groups are in the para position relative to the point of attachment of the amide linker .. In certain embodiments, one ^{R B} groups are substituted or unsubstituted _{C 1-6} alkyl. In certain embodiments, one ^{R B} groups are _{C 1-6} alkyl substituted with one -CN group. In certain embodiments, one ^{R B} group,

Is. In certain embodiments, one ^{R B} group, a substituted or unsubstituted -CH ₂ - is (piperazinyl). In certain embodiments, one ^{R B} group,

And here, the alkyl is optionally substituted. In certain embodiments, one ^{R B} group,

And here, the alkyl is unsubstituted. In certain embodiments, one ^{R B} group,

Is. In certain embodiments, one R ^B groups are haloalkyl. In certain embodiments, one ^{R B} groups are -CF _3. In certain embodiments, one R ^B groups are substituted or unsubstituted imidazolyl. In certain embodiments, one ^{R B} group,

And here, the alkyl is optionally substituted. In certain embodiments, one ^{R B} group,

And here, the alkyl is unsubstituted. In certain embodiments, one ^{R B} group,

Is. In certain embodiments, one R ^B groups are substituted or unsubstituted piperazinyl. In certain embodiments, one ^{R B} group,

And here, the alkyl is optionally substituted. In certain embodiments, one ^{R B} group,

And here, the alkyl is unsubstituted. In certain embodiments, one ^{R B} group,

Is. In certain embodiments, one R ^B groups are substituted or unsubstituted morpholine. In some embodiments, two R ^B groups are substituted or unsubstituted morpholine. In some embodiments, all cases of ^{RXc are hydrogen.} In some embodiments, ^RXa is a substituted or unsubstituted C _1-6 alkyl. In some embodiments, ^RXa is methyl or ethyl.

の化合物であって、式中、Ｒ^Ｘａ、Ｒ^Ｘｃ、Ｒ^ＡおよびＲ^Ｂは、本明細書において定義される。ある態様において、Ｒ^Ａは、置換または未置換Ｃ_１−６アルキルである。ある態様において、Ｒ^Ａは、メチルである。ある態様において、１個のＲ^Ｂ基は、置換または未置換Ｃ_１−６アルキルである。ある態様において、１個のＲ^Ｂ基は、１個の−ＣＮ基で置換されたＣ_１−６アルキルである。ある態様において、１個のＲ^Ｂ基は、

である。ある態様において、１個のＲ^Ｂ基は、置換または未置換−ＣＨ_２−（ピペラジニル）である。ある態様において、１個のＲ^Ｂ基は、

であって、ここで、アルキルは、任意に置換されている。ある態様において、１個のＲ^Ｂ基は、

であって、ここで、アルキルは、未置換である。ある態様において、１個のＲ^Ｂ基は、

である。ある態様において、１個のＲ^Ｂ基は、ハロアルキルである。ある態様において、１個のＲ^Ｂ基は、−ＣＦ_３である。ある態様において、１個のＲ^Ｂ基は、置換または未置換イミダゾリルである。ある態様において、１個のＲ^Ｂ基は、

であって、ここで、アルキルは、任意に置換されている。ある態様において、１個のＲ^Ｂ基は、

であって、ここで、アルキルは、未置換である。ある態様において、１個のＲ^Ｂ基は、

である。ある態様において、１個のＲ^Ｂ基は、置換または未置換ピペラジニルである。ある態様において、１個のＲ^Ｂ基は、

であって、ここで、アルキルは、任意に置換されている。ある態様において、１個のＲ^Ｂ基は、

であって、ここで、アルキルは、未置換である。ある態様において、１個のＲ^Ｂ基は、

である。ある態様において、１個のＲ^Ｂ基は、置換または未置換モルホリンである。ある態様において、２個のＲ^Ｂ基は、置換または未置換モルホリンである。ある態様において、Ｒ^Ｘｃの全ての場合は、水素である。ある態様において、Ｒ^Ｘａは、置換または未置換Ｃ_１−６アルキルである。ある態様において、Ｒ^Ｘａは、メチルまたはエチルである。 In some embodiments, the compounds of formula (A1) are of formulas (A1-e)-(A1-p):

A compound ^{wherein, R Xa, R Xc, R} A and ^{R B} are defined herein. In some embodiments, ^RA is a substituted or unsubstituted C _1-6 alkyl. In some embodiments, ^RA is methyl. In certain embodiments, one ^{R B} groups are substituted or unsubstituted _{C 1-6} alkyl. In certain embodiments, one ^{R B} groups are _{C 1-6} alkyl substituted with one -CN group. In certain embodiments, one ^{R B} group,

Is. In certain embodiments, one ^{R B} group, a substituted or unsubstituted -CH ₂ - is (piperazinyl). In certain embodiments, one ^{R B} group,

And here, the alkyl is optionally substituted. In certain embodiments, one ^{R B} group,

And here, the alkyl is unsubstituted. In certain embodiments, one ^{R B} group,

Is. In certain embodiments, one R ^B groups are haloalkyl. In certain embodiments, one ^{R B} groups are -CF _3. In certain embodiments, one R ^B groups are substituted or unsubstituted imidazolyl. In certain embodiments, one ^{R B} group,

And here, the alkyl is optionally substituted. In certain embodiments, one ^{R B} group,

And here, the alkyl is unsubstituted. In certain embodiments, one ^{R B} group,

Is. In certain embodiments, one R ^B groups are substituted or unsubstituted piperazinyl. In certain embodiments, one ^{R B} group,

And here, the alkyl is optionally substituted. In certain embodiments, one ^{R B} group,

And here, the alkyl is unsubstituted. In certain embodiments, one ^{R B} group,

Is. In certain embodiments, one R ^B groups are substituted or unsubstituted morpholine. In some embodiments, two R ^B groups are substituted or unsubstituted morpholine. In some embodiments, all cases of ^{RXc are hydrogen.} In some embodiments, ^RXa is a substituted or unsubstituted C _1-6 alkyl. In some embodiments, ^RXa is methyl or ethyl.

の化合物であって、式中、Ｒ^Ｘａ、Ｒ^Ｘｃ、Ｒ^ＡおよびＲ^Ｂは、本明細書において定義される。ある態様において、Ｒ^Ａは、置換または未置換Ｃ_１−６アルキルである。ある態様において、Ｒ^Ａは、メチルである。ある態様において、１個のＲ^Ｂ基は、置換または未置換Ｃ_１−６アルキルである。ある態様において、１個のＲ^Ｂ基は、１個の−ＣＮ基で置換されたＣ_１−６アルキルである。ある態様において、１個のＲ^Ｂ基は、

である。ある態様において、１個のＲ^Ｂ基は、置換または未置換−ＣＨ_２−（ピペラジニル）である。ある態様において、１個のＲ^Ｂ基は、

であって、ここで、アルキルは、任意に置換されている。ある態様において、１個のＲ^Ｂ基は、

であって、ここで、アルキルは、未置換である。ある態様において、１個のＲ^Ｂ基は、

である。ある態様において、１個のＲ^Ｂ基は、ハロアルキルである。ある態様において、１個のＲ^Ｂ基は、−ＣＦ_３である。ある態様において、１個のＲ^Ｂ基は、置換または未置換イミダゾリルである。ある態様において、１個のＲ^Ｂ基は、

であって、ここで、アルキルは、任意に置換されている。ある態様において、１個のＲ^Ｂ基は、

であって、ここで、アルキルは、未置換である。ある態様において、１個のＲ^Ｂ基は、

である。ある態様において、１個のＲ^Ｂ基は、置換または未置換ピペラジニルである。ある態様において、１個のＲ^Ｂ基は、

であって、ここで、アルキルは、任意に置換されている。ある態様において、１個のＲ^Ｂ基は、

であって、ここで、アルキルは、未置換である。ある態様において、１個のＲ^Ｂ基は、

である。ある態様において、１個のＲ^Ｂ基は、置換または未置換モルホリンである。ある態様において、２個のＲ^Ｂ基は、置換または未置換モルホリンである。ある態様において、Ｒ^Ｘｃの全ての場合は、水素である。ある態様において、Ｒ^Ｘａは、置換または未置換Ｃ_１−６アルキルである。ある態様において、Ｒ^Ｘａは、メチルまたはエチルである。 In some embodiments, the compounds of formula (A2) are of formulas (A2-e)-(A2-p):

A compound ^{wherein, R Xa, R Xc, R} A and ^{R B} are defined herein. In some embodiments, ^RA is a substituted or unsubstituted C _1-6 alkyl. In some embodiments, ^RA is methyl. In certain embodiments, one ^{R B} groups are substituted or unsubstituted _{C 1-6} alkyl. In certain embodiments, one ^{R B} groups are _{C 1-6} alkyl substituted with one -CN group. In certain embodiments, one ^{R B} group,

Is. In certain embodiments, one ^{R B} group, a substituted or unsubstituted -CH ₂ - is (piperazinyl). In certain embodiments, one ^{R B} group,

And here, the alkyl is optionally substituted. In certain embodiments, one ^{R B} group,

And here, the alkyl is unsubstituted. In certain embodiments, one ^{R B} group,

Is. In certain embodiments, one R ^B groups are haloalkyl. In certain embodiments, one ^{R B} groups are -CF _3. In certain embodiments, one R ^B groups are substituted or unsubstituted imidazolyl. In certain embodiments, one ^{R B} group,

And here, the alkyl is optionally substituted. In certain embodiments, one ^{R B} group,

And here, the alkyl is unsubstituted. In certain embodiments, one ^{R B} group,

Is. In certain embodiments, one R ^B groups are substituted or unsubstituted piperazinyl. In certain embodiments, one ^{R B} group,

And here, the alkyl is optionally substituted. In certain embodiments, one ^{R B} group,

And here, the alkyl is unsubstituted. In certain embodiments, one ^{R B} group,

Is. In certain embodiments, one R ^B groups are substituted or unsubstituted morpholine. In some embodiments, two R ^B groups are substituted or unsubstituted morpholine. In some embodiments, all cases of ^{RXc are hydrogen.} In some embodiments, ^RXa is a substituted or unsubstituted C _1-6 alkyl. In some embodiments, ^RXa is methyl or ethyl.

の化合物であり、式中、Ｒ^Ｄ、Ｒ^Ａ、Ｒ^Ｂおよびｌは本明細書において定義されるとおりである。ある態様において、Ｒ^Ａは、置換または未置換のＣ_１−６アルキルである。ある態様において、Ｒ^Ａはメチルである。ある態様において、ｌは１である。ある態様において、ｌが１であり；およびＲ^Ｂは、アミドリンカーの結合点に対してメタ位にある。ある態様において、ｌは２である。ある態様において、ｌが２であり；および２個のＲ^Ｂ基は、アミドリンカーの結合点に対してメタ位にある。ある態様において、ｌが２であり；および１個のＲ^Ｂ基はアミドリンカーの結合点に対してメタ位にあり；第２のＲ^Ｂ基は、アミドリンカーの結合点に対してパラ位にある。ある態様において、１個のＲ^Ｂ基は置換または未置換のＣ_１−６アルキルである。ある態様において、１個のＲ^Ｂ基は、１個の−ＣＮ基で置換されたＣ_１−６アルキルである。ある態様において、１個のＲ^Ｂ基は

である。ある態様において、１個のＲ^Ｂ基は、置換または未置換の−ＣＨ_２−（ピペラジニル）である。ある態様において、１個のＲ^Ｂ基は、

であり、ここで当該アルキルは任意に置換されている。ある態様において、１個のＲ^Ｂ基は、

であり、ここで当該アルキルは未置換である。ある態様において、１個のＲ^Ｂ基は

である。ある態様において、１個のＲ^Ｂ基はハロアルキルである。ある態様において、１個のＲ^Ｂ基は、−ＣＦ_３である。ある態様において、１個のＲ^Ｂ基は、置換または未置換イミダゾールである。ある態様において、１個のＲ^Ｂ基は

であり、ここで当該アルキルは、任意に置換されている。ある態様において、１個のＲ^Ｂ基は

であり、ここで当該アルキルは、未置換である。ある態様において、１個のＲ^Ｂ基は

である。ある態様において、１個のＲ^Ｂ基は、置換または未置換ピペラジニルである。ある態様において、１個のＲ^Ｂ基は、

であり、ここで当該アルキルは任意に置換されている。ある態様において、１個のＲ^Ｂ基は

であり、ここで当該アルキルは未置換である。ある態様において、１個のＲ^Ｂ基は

である。ある態様において、１個のＲ^Ｂ基は、置換または未置換のモルホリンである。ある態様において、２個のＲ^Ｂ基は置換または未置換のモルホリンである。ある態様において、Ｒ^Ｄは

である。ある態様において、Ｒ^Ｄは

である。ある態様において、Ｒ^Ｄは

である。ある態様において、Ｒ^Ｄは

である。 In some embodiments, the compounds of formula (A) are of formula (A3) or (A4) :.

In the formula, R ^D , R ^A , R ^B and l are as defined herein. In some embodiments, ^RA is a substituted or unsubstituted C _1-6 alkyl. In some embodiments, ^RA is methyl. In some embodiments, l is 1. In some embodiments, l is 1; and R ^B is meta to the point of attachment of the amide linker. In some embodiments, l is 2. In some embodiments, l is 2; and two R ^B groups are in the meta position relative to the point of attachment of the amide linker. In some embodiments, l is 2; located meta to and one R ^B groups the point of attachment of the amide linker; second R ^B groups are in the para position relative to the point of attachment of the amide linker is there. In certain embodiments, one ^{R B} groups are _{C 1-6} alkyl substituted or unsubstituted. In certain embodiments, one ^{R B} groups are _{C 1-6} alkyl substituted with one -CN group. In certain embodiments, one ^{R B} groups

Is. In certain embodiments, one ^{R B} group, -CH ₂ substituted or unsubstituted - a (piperazinyl). In certain embodiments, one ^{R B} group,

Where the alkyl is optionally substituted. In certain embodiments, one ^{R B} group,

Where the alkyl is unsubstituted. In certain embodiments, one ^{R B} groups

Is. In certain embodiments, one R ^B groups are haloalkyl. In certain embodiments, one ^{R B} groups are -CF _3. In certain embodiments, one R ^B groups are substituted or unsubstituted imidazole. In certain embodiments, one ^{R B} groups

Where the alkyl is optionally substituted. In certain embodiments, one ^{R B} groups

Where the alkyl is unsubstituted. In certain embodiments, one ^{R B} groups

Is. In certain embodiments, one R ^B groups are substituted or unsubstituted piperazinyl. In certain embodiments, one ^{R B} group,

Where the alkyl is optionally substituted. In certain embodiments, one ^{R B} groups

Where the alkyl is unsubstituted. In certain embodiments, one ^{R B} groups

Is. In certain embodiments, one R ^B groups are morpholine substituted or unsubstituted. In some embodiments, the two R ^B groups are morpholine substituted or unsubstituted. In some embodiments, ^RD is

Is. In some embodiments, ^RD is

Is. In some embodiments, ^RD is

Is. In some embodiments, ^RD is

Is.

の化合物であり、式中、Ｒ^Ｄ、Ｒ^Ａ、Ｒ^Ｂおよびｌは本明細書中に定義されるとおりである。ある態様において、Ｒ^Ａは、置換または未置換のＣ_１−６アルキルである。ある態様において、Ｒ^Ａはメチルである。ある態様において、ｌは１である。ある態様において、ｌが１であり；およびＲ^Ｂは、アミドリンカーの結合点に対してメタ位にある。ある態様において、ｌは２である。ある態様において、ｌが２であり；および２個のＲ^Ｂ基は、アミドリンカーの結合点に対してメタ位にある。ある態様において、ｌが２であり；および１個のＲ^Ｂ基はアミドリンカーの結合点に対してメタ位にあり；第２のＲ^Ｂ基は、アミドリンカーの結合点に対してパラ位にある。ある態様において、１個のＲ^Ｂ基は置換または未置換のＣ_１−６アルキルである。ある態様において、１個のＲ^Ｂ基は、１個の−ＣＮ基で置換されたＣ_１−６アルキルである。ある態様において、１個のＲ^Ｂ基は

である。ある態様において、１個のＲ^Ｂ基は、置換または未置換の−ＣＨ_２−（ピペラジニル）である。ある態様において、１個のＲ^Ｂ基は、

であり、ここで当該アルキルは任意に置換されている。ある態様において、１個のＲ^Ｂ基は、

であり、ここで当該アルキルは未置換である。ある態様において、１個のＲ^Ｂ基は、

である。ある態様において、１個のＲ^Ｂ基はハロアルキルである。ある態様において、１個のＲ^Ｂ基は、−ＣＦ_３である。ある態様において、１個のＲ^Ｂ基は、置換または未置換イミダゾールである。ある態様において、１個のＲ^Ｂ基は

であり、ここで当該アルキルは、任意に置換されている。ある態様において、１個のＲ^Ｂ基は

であり、ここで当該アルキルは、未置換である。ある態様において、１個のＲ^Ｂ基は

である。ある態様において、１個のＲ^Ｂ基は、置換または未置換ピペラジニルである。ある態様において、１個のＲ^Ｂ基は、

であり、ここで当該アルキルは任意に置換されている。ある態様において、１個のＲ^Ｂ基は

であり、ここで当該アルキルは未置換である。ある態様において、１個のＲ^Ｂ基は

である。ある態様において、１個のＲ^Ｂ基は、置換または未置換のモルホリンである。ある態様において、２個のＲ^Ｂ基は置換または未置換のモルホリンである。ある態様において、Ｒ^Ｄは

である。ある態様において、Ｒ^Ｄは

である。ある態様において、Ｒ^Ｄは

である。ある態様において、Ｒ^Ｄは

である。 In some embodiments, the compounds of formula (A3) are of formula (A3-a), (A3-b) or (A3-c) :.

In the formula, R ^D , R ^A , R ^B and l are as defined herein. In some embodiments, ^RA is a substituted or unsubstituted C _1-6 alkyl. In some embodiments, ^RA is methyl. In some embodiments, l is 1. In some embodiments, l is 1; and R ^B is meta to the point of attachment of the amide linker. In some embodiments, l is 2. In some embodiments, l is 2; and two R ^B groups are in the meta position relative to the point of attachment of the amide linker. In some embodiments, l is 2; located meta to and one R ^B groups the point of attachment of the amide linker; second R ^B groups are in the para position relative to the point of attachment of the amide linker is there. In certain embodiments, one ^{R B} groups are _{C 1-6} alkyl substituted or unsubstituted. In certain embodiments, one ^{R B} groups are _{C 1-6} alkyl substituted with one -CN group. In certain embodiments, one ^{R B} groups

Is. In certain embodiments, one ^{R B} group, -CH ₂ substituted or unsubstituted - a (piperazinyl). In certain embodiments, one ^{R B} group,

Where the alkyl is optionally substituted. In certain embodiments, one ^{R B} group,

Where the alkyl is unsubstituted. In certain embodiments, one ^{R B} group,

Is. In certain embodiments, one R ^B groups are haloalkyl. In certain embodiments, one ^{R B} groups are -CF _3. In certain embodiments, one R ^B groups are substituted or unsubstituted imidazole. In certain embodiments, one ^{R B} groups

Where the alkyl is optionally substituted. In certain embodiments, one ^{R B} groups

Where the alkyl is unsubstituted. In certain embodiments, one ^{R B} groups

Is. In certain embodiments, one R ^B groups are substituted or unsubstituted piperazinyl. In certain embodiments, one ^{R B} group,

Where the alkyl is optionally substituted. In certain embodiments, one ^{R B} groups

Where the alkyl is unsubstituted. In certain embodiments, one ^{R B} groups

Is. In certain embodiments, one R ^B groups are morpholine substituted or unsubstituted. In some embodiments, the two R ^B groups are morpholine substituted or unsubstituted. In some embodiments, ^RD is

Is. In some embodiments, ^RD is

Is. In some embodiments, ^RD is

Is. In some embodiments, ^RD is

Is.

の化合物であり、式中、Ｒ^Ｄ、Ｒ^Ａ、Ｒ^Ｂおよびｌは本明細書中に定義されるとおりである。ある態様において、Ｒ^Ａは、置換または未置換のＣ_１−６アルキルである。ある態様において、Ｒ^Ａはメチルである。ある態様において、ｌは１である。ある態様において、ｌが１であり；およびＲ^Ｂは、アミドリンカーの結合点に対してメタ位にある。ある態様において、ｌは２である。ある態様において、ｌが２であり；および２個のＲ^Ｂ基は、アミドリンカーの結合点に対してメタ位にある。ある態様において、ｌが２であり；および１個のＲ^Ｂ基はアミドリンカーの結合点に対してメタ位にあり；第２のＲ^Ｂ基は、アミドリンカーの結合点に対してパラ位にある。ある態様において、１個のＲ^Ｂ基は置換または未置換のＣ_１−６アルキルである。ある態様において、１個のＲ^Ｂ基は、１個の−ＣＮ基で置換されたＣ_１−６アルキルである。ある態様において、１個のＲ^Ｂ基は

である。ある態様において、１個のＲ^Ｂ基は、置換または未置換の−ＣＨ_２−（ピペラジニル）である。ある態様において、１個のＲ^Ｂ基は、

であり、ここで当該アルキルは任意に置換されている。ある態様において、１個のＲ^Ｂ基は、

であり、ここで当該アルキルは未置換である。ある態様において、１個のＲ^Ｂ基は、

である。ある態様において、１個のＲ^Ｂ基はハロアルキルである。ある態様において、１個のＲ^Ｂ基は、−ＣＦ_３である。ある態様において、１個のＲ^Ｂ基は、置換または未置換イミダゾールである。ある態様において、１個のＲ^Ｂ基は

であり、ここで当該アルキルは、任意に置換されている。ある態様において、１個のＲ^Ｂ基は

であり、ここで当該アルキルは、未置換である。ある態様において、１個のＲ^Ｂ基は

である。ある態様において、１個のＲ^Ｂ基は、置換または未置換ピペラジニルである。ある態様において、１個のＲ^Ｂ基は、

であり、ここで当該アルキルは任意に置換されている。ある態様において、１個のＲ^Ｂ基は

であり、ここで当該アルキルは未置換である。ある態様において、１個のＲ^Ｂ基は

である。ある態様において、１個のＲ^Ｂ基は、置換または未置換のモルホリンである。ある態様において、２個のＲ^Ｂ基は置換または未置換のモルホリンである。ある態様において、Ｒ^Ｄは

である。ある態様において、Ｒ^Ｄは

である。ある態様において、Ｒ^Ｄは

である。ある態様において、Ｒ^Ｄは

である。 In some embodiments, the compounds of formula (A4) are of formula (A4-a), (A4-b) or (A4-c) :.

In the formula, R ^D , R ^A , R ^B and l are as defined herein. In some embodiments, ^RA is a substituted or unsubstituted C _1-6 alkyl. In some embodiments, ^RA is methyl. In some embodiments, l is 1. In some embodiments, l is 1; and R ^B is meta to the point of attachment of the amide linker. In some embodiments, l is 2. In some embodiments, l is 2; and two R ^B groups are in the meta position relative to the point of attachment of the amide linker. In some embodiments, l is 2; located meta to and one R ^B groups the point of attachment of the amide linker; second R ^B groups are in the para position relative to the point of attachment of the amide linker is there. In certain embodiments, one ^{R B} groups are _{C 1-6} alkyl substituted or unsubstituted. In certain embodiments, one ^{R B} groups are _{C 1-6} alkyl substituted with one -CN group. In certain embodiments, one ^{R B} groups

Is. In certain embodiments, one ^{R B} group, -CH ₂ substituted or unsubstituted - a (piperazinyl). In certain embodiments, one ^{R B} group,

Where the alkyl is optionally substituted. In certain embodiments, one ^{R B} group,

Where the alkyl is unsubstituted. In certain embodiments, one ^{R B} group,

Is. In certain embodiments, one R ^B groups are haloalkyl. In certain embodiments, one ^{R B} groups are -CF _3. In certain embodiments, one R ^B groups are substituted or unsubstituted imidazole. In certain embodiments, one ^{R B} groups

Where the alkyl is optionally substituted. In certain embodiments, one ^{R B} groups

Where the alkyl is unsubstituted. In certain embodiments, one ^{R B} groups

Is. In certain embodiments, one R ^B groups are substituted or unsubstituted piperazinyl. In certain embodiments, one ^{R B} group,

Where the alkyl is optionally substituted. In certain embodiments, one ^{R B} groups

Where the alkyl is unsubstituted. In certain embodiments, one ^{R B} groups

Is. In certain embodiments, one R ^B groups are morpholine substituted or unsubstituted. In some embodiments, the two R ^B groups are morpholine substituted or unsubstituted. In some embodiments, ^RD is

Is. In some embodiments, ^RD is

Is. In some embodiments, ^RD is

Is. In some embodiments, ^RD is

Is.

の化合物およびその医薬的に許容可能な塩、溶媒和物、水和物、多形、共結晶、互変異性体、立体異性体、同位体標識された誘導体およびプロドラッグに関する。 Another aspect of the present invention is the formula (I-11) :.

And pharmaceutically acceptable salts thereof, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotope-labeled derivatives and prodrugs thereof.

の化合物、ならびにその医薬的に許容可能な塩、溶媒和物、水和物、多形、共結晶、互変異性体、立体異性体、同位体標識された誘導体およびプロドラッグであって；式中：
Ｒ^Ａ’、Ｒ^Ｂ’、およびＲ^Ｘ’の各々の場合は、独立して、水素、ハロゲン、任意置換のアルキル、任意置換のアルケニル、任意置換のアルキニル、任意置換のカルボシクリル、任意置換のヘテロシクリル、任意置換のアリール、任意置換のヘテロアリール、−ＯＲ^Ａ１’、−Ｎ（Ｒ^Ａ１’）_２、−ＳＲ^Ａ１’、−ＣＮ、−Ｃ（＝Ｏ）Ｒ^Ａ１’、−Ｃ（＝Ｏ）ＯＲ^Ａ１’、−Ｃ（＝Ｏ）ＳＲ^Ａ１’、−Ｃ（＝Ｏ）Ｎ（Ｒ^Ａ１’）_２、−Ｃ（＝Ｓ）Ｒ^Ａ１’、−Ｃ（＝Ｓ）ＯＲ^Ａ１’、−Ｃ（＝Ｓ）ＳＲ^Ａ１’、−Ｃ（＝Ｓ）Ｎ（Ｒ^Ａ１’）_２、−Ｃ（＝ＮＲ^Ａ１’）Ｒ^Ａ１’、−Ｃ（＝ＮＲ^Ａ１’）ＯＲ^Ａ１’、−Ｃ（＝ＮＲ^Ａ１’）ＳＲ^Ａ１’、−Ｃ（＝ＮＲ^Ａ１’）Ｎ（Ｒ^Ａ１’）_２、−ＮＯ_２、−Ｎ_３、−Ｎ（Ｒ^Ａ１’）_３ ^＋Ｘ’⁻、ここでＸ’⁻は対イオンである、−Ｎ（ＯＲ^Ａ１’）Ｒ^Ａ１’、−ＮＲ^Ａ１’Ｃ（＝Ｏ）Ｒ^Ａ１’、−ＮＲ^Ａ１’Ｃ（＝Ｏ）ＯＲ^Ａ１’、−ＮＲ^Ａ１’Ｃ（＝Ｏ）ＳＲ^Ａ１’、−ＮＲ^Ａ１’Ｃ（＝Ｏ）Ｎ（Ｒ^Ａ１’）_２、−ＮＲ^Ａ１’Ｃ（＝Ｓ）Ｒ^Ａ１’、−ＮＲ^Ａ１’Ｃ（＝Ｓ）ＯＲ^Ａ１’、−ＮＲ^Ａ１’Ｃ（＝Ｓ）ＳＲ^Ａ１’、−ＮＲ^Ａ１’Ｃ（＝Ｓ）Ｎ（Ｒ^Ａ１’）_２、−ＮＲ^Ａ１’Ｃ（＝ＮＲ^Ａ１’）Ｒ^Ａ１’、−ＮＲ^Ａ１’Ｃ（＝ＮＲ^Ａ１’）ＯＲ^Ａ１’、−ＮＲ^Ａ１’Ｃ（＝ＮＲ^Ａ１’）ＳＲ^Ａ１’、−ＮＲ^Ａ１’Ｃ（＝ＮＲ^Ａ１’）Ｎ（Ｒ^Ａ１’）_２、−ＮＲ^Ａ１’Ｓ（＝Ｏ）_２Ｒ^Ａ１’、−ＮＲ^Ａ１’Ｓ（＝Ｏ）_２ＯＲ^Ａ１’、−ＮＲ^Ａ１’Ｓ（＝Ｏ）_２ＳＲ^Ａ１’、−ＮＲ^Ａ１’Ｓ（＝Ｏ）_２Ｎ（Ｒ^Ａ１’）_２、−ＮＲ^Ａ１’Ｓ（＝Ｏ）Ｒ^Ａ１’、−ＮＲ^Ａ１’Ｓ（＝Ｏ）ＯＲ^Ａ１’、−ＮＲ^Ａ１’Ｓ（＝Ｏ）ＳＲ^Ａ１’、−ＮＲ^Ａ１’Ｓ（＝Ｏ）Ｎ（Ｒ^Ａ１’）_２、−ＮＲ^Ａ１’Ｐ（＝Ｏ）、−ＮＲ^Ａ１’Ｐ（＝Ｏ）_２、−ＮＲ^Ａ１’Ｐ（＝Ｏ）（Ｒ^Ａ１’）_２、−ＮＲ^Ａ１’Ｐ（＝Ｏ）Ｒ^Ａ１’（ＯＲ^Ａ１’）、−ＮＲ^Ａ１’Ｐ（＝Ｏ）（ＯＲ^Ａ１’）_２、−ＯＣ（＝Ｏ）Ｒ^Ａ１’、−ＯＣ（＝Ｏ）ＯＲ^Ａ１’、−ＯＣ（＝Ｏ）ＳＲ^Ａ１’、−ＯＣ（＝Ｏ）Ｎ（Ｒ^Ａ１’）_２、−ＯＣ（＝ＮＲ^Ａ１’）Ｒ^Ａ１’、−ＯＣ（＝ＮＲ^Ａ１’）ＯＲ^Ａ１’、−ＯＣ（＝ＮＲ^Ａ１’）Ｎ（Ｒ^Ａ１’）_２、−ＯＣ（＝Ｓ）Ｒ^Ａ１’、−ＯＣ（＝Ｓ）ＯＲ^Ａ１’、−ＯＣ（＝Ｓ）ＳＲ^Ａ１’、−ＯＣ（＝Ｓ）Ｎ（Ｒ^Ａ１’）_２、−ＯＮ（Ｒ^Ａ１’）_２、−ＯＳ（＝Ｏ）Ｒ^Ａ１’、−ＯＳ（＝Ｏ）ＯＲ^Ａ１’、−ＯＳ（＝Ｏ）ＳＲ^Ａ１’、−ＯＳ（＝Ｏ）Ｎ（Ｒ^Ａ１’）_２、−ＯＳ（＝Ｏ）_２Ｒ^Ａ１’、−ＯＳ（＝Ｏ）_２ＯＲ^Ａ１’、−ＯＳ（＝Ｏ）_２ＳＲ^Ａ１’、−ＯＳ（＝Ｏ）_２Ｎ（Ｒ^Ａ１’）_２、−ＯＰ（＝Ｏ）_２、−ＯＰ（＝Ｏ）（Ｒ^Ａ１’）_２、−ＯＰ（＝Ｏ）Ｒ^Ａ１’（ＯＲ^Ａ１’）、−ＯＰ（＝Ｏ）（ＯＲ^Ａ１’）_２、−ＯＰ（＝Ｏ）、−ＯＰ（Ｒ^Ａ１’）_２、−ＯＰＲ^Ａ１’（ＯＲ^Ａ１’）、−ＯＰ（ＯＲ^Ａ１’）_２、−ＯＳｉ（Ｒ^Ａ１’）_３、−ＯＳｉ（Ｒ^Ａ１’）_２ＯＲ^Ａ１’、−ＯＳｉ（Ｒ^Ａ１’）（ＯＲ^Ａ１’）_２、−ＯＳｉ（ＯＲ^Ａ１’）_３、−ＳＳＲ^Ａ１’、−Ｓ（＝Ｏ）Ｒ^Ａ１’、−Ｓ（＝Ｏ）ＯＲ^Ａ１’、−Ｓ（＝Ｏ）Ｎ（Ｒ^Ａ１’）_２、−Ｓ（＝Ｏ）_２Ｒ^Ａ１’、−Ｓ（＝Ｏ）_２ＯＲ^Ａ１’、−Ｓ（＝Ｏ）_２Ｎ（Ｒ^Ａ１’）_２、−ＳＣ（＝Ｏ）Ｒ^Ａ１’、−ＳＣ（＝Ｏ）ＯＲ^Ａ１’、−ＳＣ（＝Ｏ）ＳＲ^Ａ１’、−ＳＣ（＝Ｏ）Ｎ（Ｒ^Ａ１’）_２、−ＳＣ（＝Ｓ）Ｒ^Ａ１’、−ＳＣ（＝Ｓ）ＯＲ^Ａ１’、−ＳＣ（＝Ｓ）ＳＲ^Ａ１’、−ＳＣ（＝Ｓ）Ｎ（Ｒ^Ａ１’）_２、−Ｐ（Ｒ^Ａ１’）_２、−ＰＲ^Ａ１’（ＯＲ^Ａ１’）、−Ｐ（ＯＲ^Ａ１’）_２、−Ｐ（＝Ｏ）、−Ｐ（＝Ｏ）（Ｒ^Ａ１’）_２、−Ｐ（＝Ｏ）（ＯＲ^Ａ１’）_２、−Ｐ（＝Ｏ）Ｒ^Ａ１’（ＯＲ^Ａ１’）、−Ｐ（＝Ｏ）_２、−Ｂ（Ｒ^Ａ１’）_２、−Ｂ（ＯＲ^Ａ１’）_２、−ＢＲ^Ａ１’（ＯＲ^Ａ１’）、−Ｓｉ（Ｒ^Ａ１’）_３、−Ｓｉ（Ｒ^Ａ１’）_２ＯＲ^Ａ１’、−ＳｉＲ^Ａ１’（ＯＲ^Ａ１’）_２、および−Ｓｉ（ＯＲ^Ａ１’）_３からなる群より選択され、２個のＲ^Ａ’またはＲ^Ｂ’基は、連結されて、任意に置換された炭素環式環、任意に置換されたヘテロ環式環、任意置換のアリール、または任意置換のヘテロアリール環を形成するか、あるいはＲ^Ａ’またはＲ^Ｂ’は、Ｘ’、Ｙ’、Ｚ’、Ｑ’、Ｕ’またはＣｙのいずれか一つと共に任意の５〜８員の環を形成し；ここでＲ^Ａ１’の各々の出現は、独立して、水素、任意置換のアシル、任意置換のアルキル、任意置換のアルケニル、任意置換のアルキニル、任意置換のカルボシクリル、任意置換のヘテロシクリル、任意置換のアリール、任意置換のヘテロアリール、窒素原子に結合している場合は窒素保護基、酸素原子に結合している場合は酸素保護基、および硫黄原子に結合している場合は硫黄保護基からなる群より選択されるか、または２個のＲ^Ａ１’基は、連結されて、任意に置換されたヘテロ環式環を形成し；
ｋ’およびｌ’は、各々独立して、０、１、２、３、４または５であり；
Ｘ’、Ｙ’、Ｚ’は、各々独立して、−ＣＨ_２、−ＣＨＲ^Ａ’、−ＣＨ、−Ｃ（Ｒ^Ａ’）_２、−Ｃ、−Ｎ、−ＮＲ^Ａ’、−Ｏ、−Ｓまたは−Ｃ＝Ｏ、または結合であり、任意に、Ｒ^Ａ’またはＲ^Ｂ’と共に５〜８員の環を形成してもよく；
Ｑ’およびＵ’は、各々独立して、−ＮＲ^Ａ’、−Ｏ、−Ｃ＝Ｏ、−ＮＲ^Ａ’ＣＯ、または結合であり；
環Ａ’は、任意置換のアリール、または任意置換のヘテロアリール環であり；
環Ｃ’は、任意置換のアリール環であり；ならびに
Ｃｙは、任意置換のアリール環、任意置換のヘテロアリール環、結合、または水素である。 In another aspect, the equation (V):

Compounds, as well as pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, character isomers, isotope-labeled derivatives and prodrugs thereof; formulas During:
For each of R ^A ', R ^B ', and ^RX ', independently, hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl. , optional substituted aryl, optionally substituted ^{heteroaryl, -OR A1 ', -N (R} A1') 2, -SR A1 ', -CN, -C (= O) R A1', -C (= O) OR ^A1 ', -C (= O) SR ^A1 ', -C (= O) N ( ^RA1 ') ₂ , -C (= S) R ^A1 ', -C (= S) OR ^A1 ', -C (= S) SR ^A1 ', -C (= S) N ( ^RA1 ') ₂ , -C (= NR ^A1 ') R ^A1 ', -C (= NR ^A1 ') OR ^A1 ', -C (= ^{NR A1 ') SR A1',} -C (= NR A1 ') N (R A1') 2, -NO 2, -N 3, -N (R A1 ') 3 + X' -, where X ^'- is a ^{counterion, -N (OR A1 ') R} A1', -NR A1 'C (= O) R A1', -NR A1 'C (= O) OR A1', -NR A1 'C (= ^{O) SR A1 ', -NR A1} ' C (= O) N (R A1 ') 2, -NR A1' C (= S) R A1 ', -NR A1' C (= S) OR A1 ', - ^{NR A1 'C (= S)} SR A1', -NR A1 'C (= S) N (R A1') 2, -NR A1 'C (= NR A1') R A1 ', -NR A1' C ( ^{= NR A1 ') OR A1'} , -NR A1 'C (= NR A1') SR A1 ', -NR A1' C (= NR A1 ') N (R A1') 2, -NR A1 'S (= O) ₂ R ^A1 ', -NR ^A1 'S (= O) ₂ OR ^A1 ', -NR ^A1 'S (= O) ₂ SR ^A1 ', -NR ^A1 'S (= O) ₂ N ( ^RA1 ' ) ₂ , -NR ^A1 'S (= O) R ^A1 ', -NR ^A1 'S (= O) OR ^A1 ', -NR ^A1 'S (= O) SR ^A1 ', -NR ^{A1'S (= O) _{) N (R A1 ') 2}} , -NR A1' P (= O), - NR A1 'P (= O) 2, -NR A1' P (= O) (R A1 ') 2, -NR A1' P (= O) R ^A1 '(OR ^A1 '), -NR ^A1'P (= O) (OR ^A1 ') ₂ , -OC (= O) R ^A1 ', -OC (= O) OR ^A1 ', -OC (= O) SR ^A1 ', -OC (= O) N (R) ^A1 ') ₂ , -OC (= NR ^A1 ') R ^A1 ', -OC (= NR ^A1 ') OR ^A1 ', -OC (= NR ^A1 ') N ( ^RA1 ') ₂ , -OC (= S) ^{) R A1 ', -OC (=} S) OR A1', -OC (= S) SR A1 ', -OC (= S) N (R A1') 2, -ON (R A1 ') 2, -OS ^{(= O) R A1 ',} -OS (= O) OR A1', -OS (= O) SR A1 ', -OS (= O) N (R A1') 2, -OS (= O) 2 R _{^{A1 ', -OS (= O)}} 2 OR A1', -OS (= O) 2 SR A1 ', -OS (= O) 2 N (R A1') 2, -OP (= O) 2, -OP ^{(= O) (R A1 '} ) 2, -OP (= O) R A1' (OR A1 '), - OP (= O) (OR A1') 2, -OP (= O), - OP (R _{^{A1 ') 2, -OPR A1'}} (OR A1 '), - OP (OR A1') 2, -OSi (R A1 ') 3, -OSi (R A1') 2 OR A1 ', -OSi (R A1 ') (OR ^A1 ') ₂ , -OSI (OR ^A1 ') ₃ , -SSR ^A1 ', -S (= O) R ^A1 ', -S (= O) OR ^A1 ', -S (= O) N _{^{(R A1 ') 2, -S}} (= O) 2 R A1', -S (= O) 2 OR A1 ', -S (= O) 2 N (R A1') 2, -SC (= O) ^{R A1 ', -SC (= O} ) OR A1', -SC (= O) SR A1 ', -SC (= O) N (R A1') 2, -SC (= S) R A1 ', -SC ^{(= S) OR A1 ',} -SC (= S) SR A1', -SC (= S) N (R A1 ') 2, -P (R A1') 2, -PR A1 '(OR A1') _{^{, -P (OR A1 ') 2}} , -P (= O), - P (= O) (R A1') 2, -P (= O) (OR A1 ') 2, -P (= O) R ^{A1 '(OR A1'),} - P (= O) 2, -B (R A1 ') 2, -B (OR A1') 2, -BR A1 '(OR A1'), - Si (R A1 ' ) _{^{3, -Si (R A1 ')}} 2 OR A1', -SiR A1 '(OR A1') 2, and -Si 'is selected from the group consisting of _3, two ^{R A (OR _A1)'} or ^{R B} 'group is coupled, either to form a heteroaryl ring optionally substituted carbocyclic ring, heterocyclic ring optionally substituted, any substituted aryl or optionally substituted, or R ^a' or R ^B 'is, X', Y ', Z ', Q ', U' ring of any 5-8 membered formed with any one or Cy; each occurrence of ^{R A1} 'here, Independently to hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, nitrogen atom. It is selected from the group consisting of a nitrogen-protecting group when it is bonded, an oxygen-protecting group when it is bonded to an oxygen atom, and a sulfur-protecting group when it is bonded to a sulfur atom, or two Rs. ^{The A1'groups} are linked to form an arbitrarily substituted heterocyclic ring;
k'and l'are independently 0, 1, 2, 3, 4 or 5;
X ', Y', Z 'are each ^{_{independently, -CH 2, -CHR A',}} -CH, -C (R A ') 2, -C, -N, -NR A', -O, is -S or -C = O or a bond, optionally, may form a ring of 5-8 members with ^{R a} 'or ^{R B';}
Q 'and U' are each ^{independently, -NR A ', -O, -C} = O, -NR A' is CO or a bond;
Ring A'is an arbitrarily substituted aryl, or an arbitrarily substituted heteroaryl ring;
Ring C'is an arbitrarily substituted aryl ring; and Cy is an arbitrarily substituted aryl ring, an arbitrarily substituted heteroaryl ring, a bond, or hydrogen.

の化合物を提供し、式中、環Ｃ’、Ｃｙ、Ｑ’、Ｕ’、Ｘ’、Ｙ’、Ｚ’、Ｒ^Ａ’、Ｒ^Ｂ’、Ｒ^Ｘ’、ｋ’およびｌ’は、本明細書において定義されるとおりである。 Compounds of formula (V) include ^'substituted with a group, the ring A' 1 or 2 or more R ^A optionally an aryl group for. In some embodiments, if the ring A'is naphthyl, the present invention describes the formula (Va):

It provides compounds wherein ring C ', Cy, Q', U ', X', Y ', Z', R A ', R B', R X ', k' and l 'are present As defined in the specification.

の化合物を提供し、式中、環Ｃ’、Ｃｙ、Ｑ’、Ｕ’、Ｘ’、Ｙ’、Ｚ’、Ｒ^Ａ’、Ｒ^Ｂ’、Ｒ^Ｘ’、ｋ’およびｌ’は、本明細書において定義されるとおりである。 Compounds of formula (V) include ^'substituted with a group, the ring A' 1 or 2 or more R ^A optionally an aryl group for. In some embodiments, the ring A'is naphthyl and the present invention has the formula (V-b) :.

It provides compounds wherein ring C ', Cy, Q', U ', X', Y ', Z', R A ', R B', R X ', k' and l 'are present As defined in the specification.

の化合物を提供し、式中、環Ｃ’、Ｃｙ、Ｑ’、Ｕ’、Ｘ’、Ｙ’、Ｚ’、Ｒ^Ａ’、Ｒ^Ｂ’、Ｒ^Ｘ’、ｋ’およびｌ’は、本明細書において定義されるとおりである。 Compounds of formula (V) include ^'substituted with a group, the ring A' 1 or 2 or more R ^A optionally an aryl group for. In some embodiments, where ring A'is phenyl, the present invention has the formula (V-c):

It provides compounds wherein ring C ', Cy, Q', U ', X', Y ', Z', R A ', R B', R X ', k' and l 'are present As defined in the specification.

の化合物を提供し、式中、環Ｃ’、Ｃｙ、Ｑ’、Ｕ’、Ｘ’、Ｙ’、Ｚ’、Ｒ^Ａ’、Ｒ^Ｂ’、Ｒ^Ｘ’、ｋ’およびｌ’は、本明細書において定義されるとおりである。 Compounds of formula (V) include ^'substituted with a group, the ring A' 1 or 2 or more R ^A optionally an aryl group for. In some embodiments, where ring A'is phenyl, the present invention has the formula (Vd):

It provides compounds wherein ring C ', Cy, Q', U ', X', Y ', Z', R A ', R B', R X ', k' and l 'are present As defined in the specification.

の化合物を提供し、式中、環Ｃ’、Ｃｙ、Ｑ’、Ｕ’、Ｘ’、Ｙ’、Ｚ’、Ｒ^Ａ’、Ｒ^Ｂ’、Ｒ^Ｘ’、ｋ’およびｌ’は、本明細書において定義されるとおりである。 Compounds of formula (V) include ^'substituted with a group, the ring A' 1 or 2 or more R ^A optionally a heteroaryl group for. In some embodiments, if the ring A'is a pyrolopyrimidine, the present invention describes the formula (V-e):

It provides compounds wherein ring C ', Cy, Q', U ', X', Y ', Z', R A ', R B', R X ', k' and l 'are present As defined in the specification.

の化合物を提供し、式中、環Ｃ’、Ｃｙ、Ｑ’、Ｕ’、Ｘ’、Ｙ’、Ｚ’、Ｒ^Ａ’、Ｒ^Ｂ’、Ｒ^Ｘ’、ｋ’およびｌ’は、本明細書において定義されるとおりである。 Compounds of formula (V) include ^'substituted with a group, the ring A' 1 or 2 or more R ^A optionally a heteroaryl group for. In some embodiments, if the ring A'is a pyrimidine, the present invention describes the formula (V-e ^A ):

It provides compounds wherein ring C ', Cy, Q', U ', X', Y ', Z', R A ', R B', R X ', k' and l 'are present As defined in the specification.

の化合物を提供し、式中、環Ｃ’、Ｃｙ、Ｑ’、Ｕ’、Ｘ’、Ｙ’、Ｚ’、Ｒ^Ａ’、Ｒ^Ｂ’、Ｒ^Ｘ’、ｋ’およびｌ’は、本明細書において定義されるとおりである。 Compounds of formula (V) include ^'substituted with a group, the ring A' 1 or 2 or more R ^A optionally a heteroaryl group for. In some embodiments, if the ring A'is 1H-pyrazolo [3,4-d] pyrimidin-4-amine, the present invention presents the formula (V-e ^B ):

It provides compounds wherein ring C ', Cy, Q', U ', X', Y ', Z', R A ', R B', R X ', k' and l 'are present As defined in the specification.

の化合物を提供し、式中、環Ｃ’、Ｃｙ、Ｑ’、Ｕ’、Ｘ’、Ｙ’、Ｚ’、Ｒ^Ａ’、Ｒ^Ｂ’、Ｒ^Ｘ’、ｋ’およびｌ’は、本明細書において定義されるとおりである。 Compounds of formula (V) include ^'substituted with a group, the ring A' 1 or 2 or more R ^A optionally a heteroaryl group for. In some embodiments, when Ring A 'is a furo [2,3-c] pyridine-7-amine, the present invention provides a compound of formula ^(V-e C):

It provides compounds wherein ring C ', Cy, Q', U ', X', Y ', Z', R A ', R B', R X ', k' and l 'are present As defined in the specification.

の化合物を提供し、式中、環Ｃ’、Ｃｙ、Ｑ’、Ｕ’、Ｘ’、Ｙ’、Ｚ’、Ｒ^Ａ’、Ｒ^Ｂ’、Ｒ^Ｘ’、ｋ’およびｌ’は、本明細書において定義されるとおりである。 Compounds of formula (V) include ^'substituted with a group, the ring A' 1 or 2 or more R ^A optionally a heteroaryl group for. In some embodiments, where ring A'is quinazoline, the present invention describes the formula (V-e ^D ):

It provides compounds wherein ring C ', Cy, Q', U ', X', Y ', Z', R A ', R B', R X ', k' and l 'are present As defined in the specification.

の化合物を提供し、式中、環Ｃ’、Ｃｙ、Ｑ’、Ｕ’、Ｘ’、Ｙ’、Ｚ’、Ｒ^Ａ’、Ｒ^Ｂ’、Ｒ^Ｘ’、ｋ’およびｌ’は、本明細書において定義されるとおりである。 Compounds of formula (V) include ^'substituted with a group, the ring A' 1 or 2 or more R ^A optionally a heteroaryl group for. In some embodiments, where ring A'is phenyl and at least one ^RA ' group is linked to Cy to form any 5-8 membered ring, the present invention relates to formula (Vf):

It provides compounds wherein ring C ', Cy, Q', U ', X', Y ', Z', R A ', R B', R X ', k' and l 'are present As defined in the specification.

の化合物を提供し、式中、環Ｃ’、Ｃｙ、Ｑ’、Ｕ’、Ｘ’、Ｙ’、Ｚ’、Ｒ^Ａ’、Ｒ^Ｂ’、Ｒ^Ｘ’、ｋ’およびｌ’は、本明細書において定義されるとおりである。 Compounds of formula (V) include ^'substituted with a group, the ring A' 1 or 2 or more R ^A optionally a heteroaryl group for. In some embodiments, where ring A'is phenyl and at least one ^RA ' group is linked to Cy to form any 5-8 membered ring, the present invention is of formula (V-g) :.

It provides compounds wherein ring C ', Cy, Q', U ', X', Y ', Z', R A ', R B', R X ', k' and l 'are present As defined in the specification.

の化合物、ならびにその医薬的に許容可能な塩、溶媒和物、水和物、多形、共結晶、互変異性体、立体異性体、同位体標識された誘導体およびプロドラッグであり；式中：
Ｒ^Ｄ’の各々の場合は、独立して、Ｃｙ、環Ａ’または環Ｃ’に結合することができる任意の求電子部分であり；
ｍ’の各々の場合は、独立して、０または１であり；ならびに
環Ａ’、環Ｃ’、Ｃｙ、Ｑ’、Ｕ’、Ｘ’、Ｙ’、Ｚ’、Ｒ^Ａ’、Ｒ^Ｂ’、Ｒ^Ｘ’、ｋ’およびｌ’は、本明細書において定義されるとおりである。 In another aspect, provided herein is Formula (II) :.

Compounds, as well as pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, character isomers, isotope-labeled derivatives and prodrugs thereof; in the formula. :
Each case of R ^D' is any electrophilic moiety that can independently bind to Cy, ring A'or ring C';
'For each, independently, 0 or 1; and the ring A' m, ring C ', Cy, Q', U ', X', Y ', Z', R A ', R B ', ^RX ', k'and l'are as defined herein.

のいずれか一つであり；式中：
Ｒ^Ｄ１’は、水素、ハロゲン、任意置換のアシル、任意置換のアルキル、任意置換のアルケニル、任意置換のアルキニル、任意置換のカルボシクリル、任意置換のヘテロシクリル、任意置換のアリール、任意置換のヘテロアリール、−ＣＮ、−ＮＯ_２、−ＯＲ^Ｄ１ａ’、−Ｎ（Ｒ^Ｄ１ａ’）_２、−ＳＲ^Ｄ１ａ’、−ＣＨ_２ＯＲ^Ｄ１ａ’、−ＣＨ_２Ｎ（Ｒ^Ｄ１ａ’）_２、−ＣＨ_２ＳＲ^Ｄ１ａ’、−Ｃ（＝Ｏ）Ｒ^Ｄ１ａ’、−Ｃ（＝Ｏ）ＯＲ^Ｄ１ａ’、−Ｃ（＝Ｏ）ＳＲ^Ｄ１ａ’、−Ｃ（＝Ｏ）Ｎ（Ｒ^Ｄ１ａ’）_２、−Ｃ（＝Ｓ）Ｒ^Ｄ１ａ’、−Ｃ（＝Ｓ）ＯＲ^Ｄ１ａ’、−Ｃ（＝Ｓ）ＳＲ^Ｄ１ａ’、−Ｃ（＝Ｓ）Ｎ（Ｒ^Ｄ１ａ’）_２、−Ｃ（＝ＮＲ^Ｄ１ａ’）Ｒ^Ｄ１ａ’、−Ｃ（＝ＮＲ^Ｄ１ａ’）ＯＲ^Ｄ１ａ’、−Ｃ（＝ＮＲ^Ｄ１ａ’）ＳＲ^Ｄ１ａ’、および−Ｃ（＝ＮＲ^Ｄ１ａ’）Ｎ（Ｒ^Ｄ１ａ’）_２からなる群より選択され、ここでＲ^Ｄ１ａ’の各々の出現は、独立して、水素、任意置換のアルキル、任意置換のアルケニル、任意置換のアルキニル、任意置換のカルボシクリル、任意置換のヘテロシクリル、任意置換のアリール、および任意置換のヘテロアリールからなる群より選択されるか、または２個のＲ^Ｄ１ａ’基は、連結されて、任意に置換されたヘテロ環式環を形成し；
Ｒ^Ｄ２’は、水素、ハロゲン、任意置換のアシル、任意置換のアルキル、任意置換のアルケニル、任意置換のアルキニル、任意置換のカルボシクリル、任意置換のヘテロシクリル、任意置換のアリール、任意置換のヘテロアリール、−ＣＮ、−ＮＯ_２、−ＯＲ^Ｄ２ａ’、−Ｎ（Ｒ^Ｄ２ａ’）_２、−ＳＲ^Ｄ２ａ’、−ＣＨ_２ＯＲ^Ｄ２ａ’、−ＣＨ_２Ｎ（Ｒ^Ｄ２ａ’）_２、−ＣＨ_２ＳＲ^Ｄ２ａ’、−Ｃ（＝Ｏ）Ｒ^Ｄ２ａ’、−Ｃ（＝Ｏ）ＯＲ^Ｄ２ａ’、−Ｃ（＝Ｏ）ＳＲ^Ｄ２ａ’、−Ｃ（＝Ｏ）Ｎ（Ｒ^Ｄ２ａ’）_２、−Ｃ（＝Ｓ）Ｒ^Ｄ２ａ’、−Ｃ（＝Ｓ）ＯＲ^Ｄ２ａ’、−Ｃ（＝Ｓ）ＳＲ^Ｄ２ａ’、−Ｃ（＝Ｓ）Ｎ（Ｒ^Ｄ２ａ’）_２、−Ｃ（＝ＮＲ^Ｄ２ａ’）Ｒ^Ｄ２ａ’、−Ｃ（＝ＮＲ^Ｄ２ａ’）ＯＲ^Ｄ２ａ’、−Ｃ（＝ＮＲ^Ｄ２ａ’）ＳＲ^Ｄ２ａ’、および−Ｃ（＝ＮＲ^Ｄ２ａ’）Ｎ（Ｒ^Ｄ２ａ’）_２からなる群より選択され、ここでＲ^Ｄ２ａ’の各々の出現は、独立して、水素、任意置換のアルキル、任意置換のアルケニル、任意置換のアルキニル、任意置換のカルボシクリル、任意置換のヘテロシクリル、任意置換のアリール、および任意置換のヘテロアリールからなる群より選択されるか、または２個のＲ^Ｄ２ａ’基は、連結されて、任意に置換されたヘテロ環式環を形成し；
Ｒ^Ｄ３’は、水素、ハロゲン、任意置換のアシル、任意置換のアルキル、任意置換のアルケニル、任意置換のアルキニル、任意置換のカルボシクリル、任意置換のヘテロシクリル、任意置換のアリール、任意置換のヘテロアリール、−ＣＮ、−ＮＯ_２、−ＯＲ^Ｄ３ａ’、−Ｎ（Ｒ^Ｄ３ａ’）_２、−ＳＲ^Ｄ３ａ’、−ＣＨ_２ＯＲ^Ｄ３ａ’、−ＣＨ_２Ｎ（Ｒ^Ｄ３ａ’）_２、−ＣＨ_２ＳＲ^Ｄ３ａ’、−Ｃ（＝Ｏ）Ｒ^Ｄ３ａ’、−Ｃ（＝Ｏ）ＯＲ^Ｄ３ａ’、−Ｃ（＝Ｏ）ＳＲ^Ｄ３ａ’、−Ｃ（＝Ｏ）Ｎ（Ｒ^Ｄ３ａ’）_２、−Ｃ（＝Ｓ）Ｒ^Ｄ３ａ’、−Ｃ（＝Ｓ）ＯＲ^Ｄ３ａ’、−Ｃ（＝Ｓ）ＳＲ^Ｄ３ａ’、−Ｃ（＝Ｓ）Ｎ（Ｒ^Ｄ３ａ’）_２、−Ｃ（＝ＮＲ^Ｄ３ａ’）Ｒ^Ｄ３ａ’、−Ｃ（＝ＮＲ^Ｄ３ａ’）ＯＲ^Ｄ３ａ’、−Ｃ（＝ＮＲ^Ｄ３ａ’）ＳＲ^Ｄ３ａ’、および−Ｃ（＝ＮＲ^Ｄ３ａ’）Ｎ（Ｒ^Ｄ３ａ’）_２からなる群より選択され、ここでＲ^Ｄ３ａ’の各々の出現は、独立して、水素、任意置換のアルキル、任意置換のアルケニル、任意置換のアルキニル、任意置換のカルボシクリル、任意置換のヘテロシクリル、任意置換のアリール、および任意置換のヘテロアリールからなる群より選択されるか、または２個のＲ^Ｄ３ａ’基は、連結されて、任意に置換されたヘテロ環式環を形成し；
任意に、Ｒ^Ｄ１’およびＲ^Ｄ３’、またはＲ^Ｄ２’およびＲ^Ｄ３’、またはＲ^Ｄ１’およびＲ^Ｄ２’は、連結されて、任意に置換された炭素環式環または任意に置換されたヘテロ環式環を形成し；
Ｒ^Ｄ４’は脱離基であり；
Ｒ^Ｄ５’は、水素、Ｃ_１−６アルキル、または窒素保護基であり；
Ｙ^Ｚ’は、−Ｏ、−Ｓまたは−ＮＲ^Ｄ６’であり、ここでＲ^Ｄ６’は、水素、Ｃ_１−６アルキル、または窒素保護基であり；
ａ’は、１または２であり；ならびに
ｚ’は、０、１、２、３、４、５または６である。 In some embodiments, R D ^'is, Cy, ring A''be any electrophilic moiety capable of binding to a; m' or ring C is 0 or 1. In the compounds of formula (II), R D ^'is, Cy, Ring A' is any electrophilic moiety capable of binding to or ring C '. In some embodiments, ^{R D} 'has the formula (i-1) ~ (i -17):

One of the following;
^RD1'is hydrogen, halogen, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbometricyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, -CN, -NO ₂ , -OR ^D1a ', -N ( ^RD1a ') ₂ , -SR ^D1a ', -CH ₂ OR ^D1a ', -CH ₂ N ( ^RD1a ') ₂ , -CH ₂ SR ^D1a ' , -C (= O) R ^D1a ', -C (= O) OR ^D1a ', -C (= O) SR ^D1a ', -C (= O) N ( ^RD1a ') ₂ , -C (= S) ) R ^D1a ', -C (= S) OR ^D1a ', -C (= S) SR ^D1a ', -C (= S) N ( ^RD1a ') ₂ , -C (= NR ^D1a ') R ^D1a ' , -C (= NR ^D1a ') OR ^D1a ', -C (= NR ^D1a ') SR ^D1a ', and -C (= NR ^D1a ') N ( ^RD1a ') ₂ selected from the group, where ^{Each appearance of RD1a'is} independent of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbociclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted hetero. Selected from the group consisting of aryl, or two R ^D1a'groups are linked to form an arbitrarily substituted heterocyclic ring;
^RD2'is hydrogen, halogen, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbometricyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, -CN, -NO ₂ , -OR ^D2a ', -N ( ^RD2a ') ₂ , -SR ^D2a ', -CH ₂ OR ^D2a ', -CH ₂ N ( ^RD2a ') ₂ , -CH ₂ SR ^D2a ' , -C (= O) R ^D2a ', -C (= O) OR ^D2a ', -C (= O) SR ^D2a ', -C (= O) N ( ^RD2a ') ₂ , -C (= S) ) R ^D2a ', -C (= S) OR ^D2a ', -C (= S) SR ^D2a ', -C (= S) N ( ^RD2a ') ₂ , -C (= NR ^D2a ') R ^D2a ' , -C (= NR ^D2a ') OR ^D2a ', -C (= NR ^D2a ') SR ^D2a ', and -C (= NR ^D2a ') N ( ^RD2a ') ₂ selected from the group, where Each appearance of R ^D2a'is independent of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbometricyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted hetero. Selected from the group consisting of aryl, or two R ^D2a'groups are linked to form an arbitrarily substituted heterocyclic ring;
^RD3'is hydrogen, halogen, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbometricyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, -CN, -NO ₂ , -OR ^D3a ', -N (R ^D3a ') ₂ , -SR ^D3a ', -CH ₂ OR ^D3a ', -CH ₂ N (R ^D3a ') ₂ , -CH ₂ SR ^D3a ' , -C (= O) R ^D3a ', -C (= O) OR ^D3a ', -C (= O) SR ^D3a ', -C (= O) N ( ^RD3a ') ₂ , -C (= S) ) R ^D3a ', -C (= S) OR ^D3a ', -C (= S) SR ^D3a ', -C (= S) N ( ^RD3a ') ₂ , -C (= NR ^D3a ') R ^D3a ' , -C (= NR ^D3a ') OR ^D3a ', -C (= NR ^D3a ') SR ^D3a ', and -C (= NR ^D3a ') N ( ^RD3a ') ₂ selected from the group, where Each appearance of R ^D3a'is independent of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbometricyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted hetero. Selected from the group consisting of aryl, or two ^RD3a'groups are linked to form an arbitrarily substituted heterocyclic ring;
Optionally, R ^D1'and R ^D3 ', or R ^D2'and R ^D3 ', or R ^D1'and R ^D2'are linked and optionally substituted carbocyclic rings or optionally substituted heterocycles. Form a cyclic ring;
R ^{D4'is a} leaving group;
^RD5'is a hydrogen, C _1-6 alkyl, or nitrogen protecting group;
Y ^Z 'is -O, -S or ^{-NR D6'} is, wherein ^{R D6} 'is _{hydrogen, C 1-6} alkyl or a nitrogen protecting group;
a'is 1 or 2; and z'is 0, 1, 2, 3, 4, 5 or 6.

の化合物を提供し、式中、環Ｃ’、Ｃｙ、Ｑ’、Ｕ’、Ｘ’、Ｙ’、Ｚ’、Ｒ^Ａ’、Ｒ^Ｂ’、Ｒ^Ｄ’、Ｒ^Ｘ’、ｋ’、ｌ’およびｍ’は、本明細書において定義されるとおりである。 Compounds of formula (II) include ^'substituted with a group, the ring A' 1 or 2 or more R ^A optionally an aryl group for. In some embodiments, if ring A'is naphthyl, the present invention describes formula (II-a):

In the formula, rings C', Cy, Q', U', X', Y', Z', ^RA ', R ^B ', R ^D ', ^RX ', k', l 'And m'are as defined herein.

の化合物を提供し、式中、環Ｃ’、Ｃｙ、Ｑ’、Ｕ’、Ｘ’、Ｙ’、Ｚ’、Ｒ^Ａ’、Ｒ^Ｂ’、Ｒ^Ｄ’、Ｒ^Ｘ’、ｋ’、ｌ’およびｍ’は、本明細書において定義されるとおりである。 Compounds of formula (II) include ^'substituted with a group, the ring A' 1 or 2 or more R ^A optionally an aryl group for. In some embodiments, if ring A'is naphthyl, the present invention describes formula (II-b):

In the formula, rings C', Cy, Q', U', X', Y', Z', ^RA ', R ^B ', R ^D ', ^RX ', k', l 'And m'are as defined herein.

の化合物を提供し、式中、環Ｃ’、Ｃｙ、Ｑ’、Ｕ’、Ｘ’、Ｙ’、Ｚ’、Ｒ^Ａ’、Ｒ^Ｂ’、Ｒ^Ｄ’、Ｒ^Ｘ’、ｋ’、ｌ’およびｍ’は、本明細書において定義されるとおりである。 Compounds of formula (II) include ^'substituted with a group, the ring A' 1 or 2 or more R ^A optionally an aryl group for. In some embodiments, where ring A'is phenyl, the present invention relates to formula (II-c):

In the formula, rings C', Cy, Q', U', X', Y', Z', ^RA ', R ^B ', R ^D ', ^RX ', k', l 'And m'are as defined herein.

の化合物を提供し、式中、環Ｃ’、Ｃｙ、Ｑ’、Ｕ’、Ｘ’、Ｙ’、Ｚ’、Ｒ^Ａ’、Ｒ^Ｂ’、Ｒ^Ｄ’、Ｒ^Ｘ’、ｋ’、ｌ’およびｍ’は、本明細書において定義されるとおりである。 Compounds of formula (II) include ^'substituted with a group, the ring A' 1 or 2 or more R ^A optionally an aryl group for. In some embodiments, where ring A'is phenyl, the present invention describes formula (II-d):

In the formula, rings C', Cy, Q', U', X', Y', Z', ^RA ', R ^B ', R ^D ', ^RX ', k', l 'And m'are as defined herein.

の化合物を提供し、式中、環Ｃ’、Ｃｙ、Ｑ’、Ｕ’、Ｘ’、Ｙ’、Ｚ’、Ｒ^Ａ’、Ｒ^Ｂ’、Ｒ^Ｄ’、Ｒ^Ｘ’、ｋ’、ｌ’およびｍ’は、本明細書において定義されるとおりである。 Compounds of formula (II) include ^'substituted with a group, the ring A' 1 or 2 or more R ^A optionally a heteroaryl group for. In some embodiments, if the ring A'is a pyrolopyrimidine, the present invention describes formula (II-e):

In the formula, rings C', Cy, Q', U', X', Y', Z', ^RA ', R ^B ', R ^D ', ^RX ', k', l 'And m'are as defined herein.

の化合物を提供し、式中、環Ｃ’、Ｃｙ、Ｑ’、Ｕ’、Ｘ’、Ｙ’、Ｚ’、Ｒ^Ａ’、Ｒ^Ｂ’、Ｒ^Ｄ’、Ｒ^Ｘ’、ｋ’、ｌ’およびｍ’は、本明細書において定義されるとおりである。 Compounds of formula (II) include ^'substituted with a group, the ring A' 1 or 2 or more R ^A optionally a heteroaryl group for. In some embodiments, if ring A'is a pyrimidine, the present invention is of formula (II-e ^A ) :.

In the formula, rings C', Cy, Q', U', X', Y', Z', ^RA ', R ^B ', R ^D ', ^RX ', k', l 'And m'are as defined herein.

の化合物を提供し、式中、環Ｃ’、Ｃｙ、Ｑ’、Ｕ’、Ｘ’、Ｙ’、Ｚ’、Ｒ^Ａ’、Ｒ^Ｂ’、Ｒ^Ｄ’、Ｒ^Ｘ’、ｋ’、ｌ’およびｍ’は、本明細書において定義されるとおりである。 Compounds of formula (II) include ^'substituted with a group, the ring A' 1 or 2 or more R ^A optionally a heteroaryl group for. In some embodiments, if ring A'is a pyrimidine, the present invention is of formula (II-e ^B ) :.

In the formula, rings C', Cy, Q', U', X', Y', Z', ^RA ', R ^B ', R ^D ', ^RX ', k', l 'And m'are as defined herein.

の化合物を提供し、式中、環Ｃ’、Ｃｙ、Ｑ’、Ｕ’、Ｘ’、Ｙ’、Ｚ’、Ｒ^Ａ’、Ｒ^Ｂ’、Ｒ^Ｘ’、ｋ’およびｌ’は、本明細書において定義されるとおりである。 Compounds of formula (II) include ^'substituted with a group, the ring A' 1 or 2 or more R ^A optionally a heteroaryl group for. In some embodiments, if the ring A'is a flow [2,3-c] pyridine-7-amine, the present invention is of formula (II-e ^C ):

It provides compounds wherein ring C ', Cy, Q', U ', X', Y ', Z', R A ', R B', R X ', k' and l 'are present As defined in the specification.

の化合物を提供し、式中、環Ｃ’、Ｃｙ、Ｑ’、Ｕ’、Ｘ’、Ｙ’、Ｚ’、Ｒ^Ａ’、Ｒ^Ｂ’、Ｒ^Ｘ’、ｋ’およびｌ’は、本明細書において定義されるとおりである。 Compounds of formula (II) include ^'substituted with a group, the ring A' 1 or 2 or more R ^A optionally a heteroaryl group for. In some embodiments, if ring A'is quinazoline, the present invention is of formula (II-e ^D ):

It provides compounds wherein ring C ', Cy, Q', U ', X', Y ', Z', R A ', R B', R X ', k' and l 'are present As defined in the specification.

の化合物を提供し、式中、環Ｃ’、Ｃｙ、Ｑ’、Ｕ’、Ｘ’、Ｙ’、Ｚ’、Ｒ^Ａ’、Ｒ^Ｂ’、Ｒ^Ｄ’、Ｒ^Ｘ’、ｋ’、ｌ’およびｍ’は、本明細書において定義されるとおりである。 Compounds of formula (II) include ^'substituted with a group, the ring A' 1 or 2 or more R ^A optionally a heteroaryl group for. In some embodiments, Ring A 'is phenyl, at least one of R ^A' in the case of forming any 5- to 8-membered ring group is linked to Cy, the present invention provides a compound of formula (II-f):

In the formula, rings C', Cy, Q', U', X', Y', Z', ^RA ', R ^B ', R ^D ', ^RX ', k', l 'And m'are as defined herein.

の化合物を提供し、式中、環Ｃ’、Ｃｙ、Ｑ’、Ｕ’、Ｘ’、Ｙ’、Ｚ’、Ｒ^Ａ’、Ｒ^Ｂ’、Ｒ^Ｄ’、Ｒ^Ｘ’、ｋ’、ｌ’およびｍ’は、本明細書において定義されるとおりである。 Compounds of formula (II) include ^'substituted with a group, the ring A' 1 or 2 or more R ^A optionally a heteroaryl group for. In some embodiments, Ring A 'is phenyl, at least one of R ^A' in the case of forming any 5- to 8-membered ring group is linked to Cy, the present invention provides a compound of formula (II-g):

In the formula, rings C', Cy, Q', U', X', Y', Z', ^RA ', R ^B ', R ^D ', ^RX ', k', l 'And m'are as defined herein.

In the compounds of formula (II), ^{R D} ', Ring A', is a substituent on the ring C 'or Cy. In some embodiments, R D ^'comprises a Michael acceptor moiety. This Michael acceptor moiety may react with cysteine or other nucleophilic residues to allow covalent attachment of the compound to the target. In some embodiments, covalent bonds are irreversible. In other embodiments, the covalent bond is reversible. In some embodiments, ^{R D} 'is of formula (i-1). In some embodiments, ^{R D} 'is of formula (i-2). In some embodiments, ^{R D} 'is of formula (i-3). In some embodiments, ^{R D} 'is of formula (i-4). In some embodiments, ^{R D} 'is of formula (i-5). In some embodiments, ^{R D} 'is of formula (i-6). In some embodiments, ^{R D} 'is of formula (i-7). In some embodiments, ^{R D} 'is of formula (i-8). In some embodiments, ^{R D} 'is of formula (i-9). In some embodiments, ^{R D} 'is of formula (i-10). In some embodiments, ^{R D} 'is of formula (i-11). In some embodiments, ^{R D} 'is of formula (i-12). In some embodiments, ^{R D} 'is of formula (i-13). In some embodiments, ^{R D} 'is of formula (i-14). In some embodiments, ^{R D} 'is of formula (i-15). In some embodiments, ^{R D} 'is of formula (i-16). In some embodiments, ^{R D} 'is of formula (i-17).

In the compounds of formula (II), R D 'is a substituted group R D1' may contain. In some embodiments, RD1'is H. In some embodiments, RD1'is a halogen. In some embodiments, RD1'is F. In some embodiments, R D1 'is is Cl. In some embodiments, R D1 'is Br. In some embodiments, R D1 'is I (iodine). In some embodiments, RD1'is a substituted acyl. In some embodiments, R D1 'is unsubstituted acyl. In some embodiments, R D1 'is acetyl. In some embodiments, RD1'is a substituted alkyl. In some embodiments, RD1'is an unsubstituted alkyl. In some embodiments, RD1'is C 1-6 alkyl. In some embodiments, RD1'is methyl. In some embodiments, RD1'is ethyl. In some embodiments, R D1 'is propyl. In some embodiments, RD1'is butyl. In some embodiments, R D1 'is substituted alkenyl. In some embodiments, R D1 'is unsubstituted alkenyl. In some embodiments, R D1 'is substituted alkynyl. In some embodiments, R D1 'is unsubstituted alkynyl. In some embodiments, R D1 'is a substituted carbocyclyl. In some embodiments, R D1 'is unsubstituted carbocyclyl. In some embodiments, R D1 'is a substituted heterocyclyl. In some embodiments, R D1 'is unsubstituted heterocyclyl. In some embodiments, RD1'is a substituted aryl. In some embodiments, RD1'is an unsubstituted aryl. In some embodiments, RD1'is a substituted phenyl. In some embodiments, RD1'is an unsubstituted phenyl. In some embodiments, RD1'is a substituted heteroaryl. In some embodiments, RD1'is an unsubstituted heteroaryl. In some embodiments, R D1 'is substituted pyridyl. In some embodiments, R D1 'is unsubstituted pyridyl. In some embodiments, R D1 'is -CN. In some embodiments, R D1 'is -NO 2. In some embodiments, R D1 'is OR D1a' is. In some embodiments, R D1 'is, -N (R D1a') 2. In some embodiments, R D1 'is SR D1a' is. In some embodiments, R D1 'is, -CH 2 OR D1a' is. In some embodiments, R D1 'is, -CH 2 N (R D1a' ) 2. In some embodiments, R D1 'is, -CH 2 SR D1a' is.

In some embodiments, at least one R ^D1a'is H. In some embodiments, at least one R ^D1a'is a substituted acyl. In some embodiments, at least one ^RD1a'is an unsubstituted acyl. In some embodiments, at least one ^RD1a'is acetyl. In some embodiments, at least one ^RD1a'is a substituted alkyl. In some embodiments, at least one ^RD1a'is an unsubstituted alkyl. In some embodiments, at least one ^RD1a'is C _1-6 alkyl. In some embodiments, at least one ^RD1a'is methyl. In some embodiments, at least one ^RD1a'is ethyl. In some embodiments, at least one ^RD1a'is propyl. In some embodiments, at least one ^RD1a'is butyl. In some embodiments, at least one ^RD1a'is a substituted alkenyl. In some embodiments, at least one ^RD1a'is an unsubstituted alkenyl. In some embodiments, at least one ^RD1a'is a substituted alkynyl. In some embodiments, at least one ^RD1a'is an unsubstituted alkynyl. In some embodiments, at least one R ^D1a'is a substituted carbocyclyl. In some embodiments, at least one ^RD1a'is an unsubstituted carbocyclyl. In some embodiments, at least one ^RD1a'is a substituted heterocyclyl. In some embodiments, at least one ^RD1a'is an unsubstituted heterocyclyl. In some embodiments, at least one ^RD1a'is a substituted aryl. In some embodiments, at least one ^RD1a'is an unsubstituted aryl. In some embodiments, at least one ^RD1a'is a substituted phenyl. In some embodiments, at least one ^RD1a'is an unsubstituted phenyl. In some embodiments, at least one ^RD1a'is a substituted heteroaryl. In some embodiments, at least one ^RD1a'is an unsubstituted heteroaryl. In some embodiments, at least one ^RD1a'is a substituted pyridyl. In some embodiments, at least one ^RD1a'is an unsubstituted pyridyl. In some embodiments, at least one ^RD1a'is a nitrogen protecting group if it is attached to a nitrogen atom. In some embodiments, at least one ^RD1a'is Bn, BOC, Cbz, Fmoc, trifluoroacetyl, triphenylmethyl or Ts when attached to a nitrogen atom. In some embodiments, ^RD1a'is an oxygen protecting group when attached to an oxygen atom. In some ^{embodiments, R D1a} ', if attached to an oxygen atom, is silyl, TBDPS, TBDMS, TIPS, TES , TMS, MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl or benzoyl .. In some embodiments, ^RD1a'is a sulfur protecting group when attached to a sulfur atom. In some embodiments, ^RD1a'is acetamidemethyl, t-Bu, 3-nitro-2-pyridinesulfenyl, 2-pyridine-sulphenyl or triphenylmethyl when attached to a sulfur atom. In some embodiments, the two R ^D1a'groups are linked to form a substituted heterocyclic ring. In some embodiments, the two R ^D1a'groups are linked to form an unsubstituted heterocyclic ring.

In the compounds of formula (II), R D 'is a substituted group R D2' may contain. In some embodiments, RD2'is H. In some embodiments, RD2'is a halogen. In some embodiments, RD2'is F. In some embodiments, R D2 'is is Cl. In some embodiments, R D2 'is Br. In some embodiments, R D2 'is I (iodine). In some embodiments, RD2'is a substituted acyl. In some embodiments, RD2'is an unsubstituted acyl. In some embodiments, R D2 'is acetyl. In some embodiments, RD2'is a substituted alkyl. In some embodiments, RD2'is an unsubstituted alkyl. In some embodiments, RD2'is C 1-6 alkyl. In some embodiments, RD2'is methyl. In some embodiments, RD2'is ethyl. In some embodiments, R D2 'is propyl. In some embodiments, RD2'is butyl. In some embodiments, RD2'is a substituted alkenyl. In some embodiments, R D2 'is unsubstituted alkenyl. In some embodiments, R D2 'is substituted alkynyl. In some embodiments, R D2 'is unsubstituted alkynyl. In some embodiments, R D2 'is a substituted carbocyclyl. In some embodiments, R D2 'is unsubstituted carbocyclyl. In some embodiments, R D2 'is a substituted heterocyclyl. In some embodiments, R D2 'is unsubstituted heterocyclyl. In some embodiments, RD2'is a substituted aryl. In some embodiments, RD2'is an unsubstituted aryl. In some embodiments, RD2'is a substituted phenyl. In some embodiments, RD2'is an unsubstituted phenyl. In some embodiments, RD2'is a substituted heteroaryl. In some embodiments, RD2'is an unsubstituted heteroaryl. In some embodiments, R D2 'is substituted pyridyl. In some embodiments, R D2 'is unsubstituted pyridyl. In some embodiments, R D2 'is -CN. In some embodiments, R D2 'is -NO 2. In some embodiments, R D2 'are, -OR D2a' is. In some embodiments, R D2 'is, -N (R D2a') 2. In some embodiments, R D2 'is, -SR D2a' is. In some embodiments, R D2 'is, -CH 2 OR D2a' is. In some embodiments, R D2 'is, -CH 2 N (R D2a' ) 2. In some embodiments, R D2 'is, -CH 2 SR D2a' is.

In some embodiments, at least one R ^D2a'is H. In some embodiments, at least one ^RD2a'is a substituted acyl. In some embodiments, at least one ^RD2a'is an unsubstituted acyl. In some embodiments, at least one ^RD2a'is acetyl. In some embodiments, at least one ^RD2a'is a substituted alkyl. In some embodiments, at least one ^RD2a'is an unsubstituted alkyl. In some embodiments, at least one ^RD2a'is C _1-6 alkyl. In some embodiments, at least one ^RD2a'is methyl. In some embodiments, at least one ^RD2a'is ethyl. In some embodiments, at least one ^RD2a'is propyl. In some embodiments, at least one ^RD2a'is butyl. In some embodiments, at least one ^RD2a'is a substituted alkenyl. In some embodiments, at least one ^RD2a'is an unsubstituted alkenyl. In some embodiments, at least one ^RD2a'is a substituted alkynyl. In some embodiments, at least one ^RD2a'is an unsubstituted alkynyl. In some embodiments, at least one ^RD2a'is a substituted carbocyclyl. In some embodiments, at least one ^RD2a'is an unsubstituted carbocyclyl. In some embodiments, at least one ^RD2a'is a substituted heterocyclyl. In some embodiments, at least one ^RD2a'is an unsubstituted heterocyclyl. In some embodiments, at least one ^RD2a'is a substituted aryl. In some embodiments, at least one ^RD2a'is an unsubstituted aryl. In some embodiments, at least one ^RD2a'is a substituted phenyl. In some embodiments, at least one ^RD2a'is an unsubstituted phenyl. In some embodiments, at least one ^RD2a'is a substituted heteroaryl. In some embodiments, at least one ^RD2a'is an unsubstituted heteroaryl. In some embodiments, at least one ^RD2a'is a substituted pyridyl. In some embodiments, at least one ^RD2a'is an unsubstituted pyridyl. In some embodiments, at least one ^RD2a'is a nitrogen protecting group if it is attached to a nitrogen atom. In some embodiments, at least one ^RD2a'is Bn, BOC, Cbz, Fmoc, trifluoroacetyl, triphenylmethyl or Ts when attached to a nitrogen atom. In some embodiments, ^RD2a'is an oxygen protecting group when attached to an oxygen atom. In some ^{embodiments, R D2a} ', if attached to an oxygen atom, is silyl, TBDPS, TBDMS, TIPS, TES , TMS, MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl or benzoyl .. In some embodiments, ^RD2a'is a sulfur protecting group when attached to a sulfur atom. In some embodiments, ^RD2a'is acetamide methyl, t-Bu, 3-nitro-2-pyridinesulphenyl, 2-pyridine-sulphenyl or triphenylmethyl when attached to a sulfur atom. In some embodiments, the two R ^D2a'groups are linked to form a substituted heterocyclic ring. In some embodiments, the two R ^D2a'groups are linked to form an unsubstituted heterocyclic ring.

In the compounds of formula (II), R D 'is a substituted group R D3' may contain. In some embodiments, RD3'is H. In some embodiments, RD3'is a halogen. In some embodiments, RD3'is F. In some embodiments, R D3 'is is Cl. In some embodiments, R D3 'is Br. In some embodiments, R D3 'is I (iodine). In some embodiments, RD3'is a substituted acyl. In some embodiments, RD3'is an unsubstituted acyl. In some embodiments, RD3'is acetyl. In some embodiments, RD3'is a substituted alkyl. In some embodiments, RD3'is an unsubstituted alkyl. In some embodiments, RD3'is C 1-6 alkyl. In some embodiments, RD3'is methyl. In some embodiments, RD3'is ethyl. In some embodiments, RD3'is propyl. In some embodiments, RD3'is butyl. In some embodiments, RD3'is a substituted alkenyl. In some embodiments, RD3'is an unsubstituted alkenyl. In some embodiments, RD3'is a substituted alkynyl. In some embodiments, R D3 'is unsubstituted alkynyl. In some embodiments, R D3 'is a substituted carbocyclyl. In some embodiments, R D3 'is unsubstituted carbocyclyl. In some embodiments, R D3 'is a substituted heterocyclyl. In some embodiments, R D3 'is unsubstituted heterocyclyl. In some embodiments, RD3'is a substituted aryl. In some embodiments, RD3'is an unsubstituted aryl. In some embodiments, RD3'is a substituted phenyl. In some embodiments, RD3'is an unsubstituted phenyl. In some embodiments, RD3'is a substituted heteroaryl. In some embodiments, RD3'is an unsubstituted heteroaryl. In some embodiments, R D3 'is substituted pyridyl. In some embodiments, R D3 'is unsubstituted pyridyl. In some embodiments, R D3 'is -CN. In some embodiments, R D3 'is -NO 2. In some embodiments, R D3 'are, -OR D3a' is. In some embodiments, R D3 'is, -N (R D3a') 2. In some embodiments, R D3 'is, -SR D3a' is. In some embodiments, R D3 'is, -CH 2 OR D3a' is. In some embodiments, R D3 'is, -CH 2 N (R D3a' ) 2. In some embodiments, R D3 'is, -CH 2 SR D3a' is.

In some embodiments, at least one ^RD3a'is H. In some embodiments, at least one ^RD3a'is a substituted acyl. In some embodiments, at least one ^RD3a'is an unsubstituted acyl. In some embodiments, at least one ^RD3a'is acetyl. In some embodiments, at least one ^RD3a'is a substituted alkyl. In some embodiments, at least one ^RD3a'is an unsubstituted alkyl. In some embodiments, at least one ^RD3a'is C _1-6 alkyl. In some embodiments, at least one ^RD3a'is methyl. In some embodiments, at least one ^RD3a'is ethyl. In some embodiments, at least one ^RD3a'is propyl. In some embodiments, at least one ^RD3a'is butyl. In some embodiments, at least one ^RD3a'is a substituted alkenyl. In some embodiments, at least one ^RD3a'is an unsubstituted alkenyl. In some embodiments, at least one ^RD3a'is a substituted alkynyl. In some embodiments, at least one ^RD3a'is an unsubstituted alkynyl. In some embodiments, at least one ^RD3a'is a substituted carbocyclyl. In some embodiments, at least one ^RD3a'is an unsubstituted carbocyclyl. In some embodiments, at least one ^RD3a'is a substituted heterocyclyl. In some embodiments, at least one ^RD3a'is an unsubstituted heterocyclyl. In some embodiments, at least one ^RD3a'is a substituted aryl. In some embodiments, at least one ^RD3a'is an unsubstituted aryl. In some embodiments, at least one ^RD3a'is a substituted phenyl. In some embodiments, at least one ^RD3a'is an unsubstituted phenyl. In some embodiments, at least one ^RD3a'is a substituted heteroaryl. In some embodiments, at least one ^RD3a'is an unsubstituted heteroaryl. In some embodiments, at least one ^RD3a'is a substituted pyridyl. In some embodiments, at least one ^RD3a'is an unsubstituted pyridyl. In some embodiments, at least one ^RD3a'is a nitrogen protecting group if it is attached to a nitrogen atom. In some embodiments, at least one ^RD3a'is Bn, BOC, Cbz, Fmoc, trifluoroacetyl, triphenylmethyl or Ts when attached to a nitrogen atom. In some embodiments, ^RD3a'is an oxygen protecting group when attached to an oxygen atom. In some embodiments, ^RD3a'is silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl or benzoyl when attached to an oxygen atom. .. In some embodiments, ^RD3a'is a sulfur protecting group when attached to a sulfur atom. In some embodiments, ^RD3a'is acetamide methyl, t-Bu, 3-nitro-2-pyridinesulphenyl, 2-pyridine-sulphenyl or triphenylmethyl when attached to a sulfur atom. In some embodiments, the two R ^D3a'groups are linked to form a substituted heterocyclic ring. In some embodiments, the two R ^D3a'groups are linked to form an unsubstituted heterocyclic ring.

In the compounds of formula (II), ^{R D} 'is a substituted group ^{R D4'} may contain. In some embodiments, R ^{D4 'is} a leaving group. In some embodiments, ^RD4'is a halogen. In some embodiments, ^RD4'is F. In some embodiments, ^RD4'is Cl. In some embodiments, R ^D4'is Br. In some ^{embodiments, R D4} 'is I (iodine). In some ^{embodiments, R D4} 'is, -OS (= O) _w' is R ^D4a '. In some embodiments, w'is 1. In some embodiments, w'is 2. In some ^{embodiments, R D4} 'is -OMs. In some ^{embodiments, R D4} 'is -OTf. In some ^{embodiments, R D4} 'is -OTs. In some ^{embodiments, R D4} 'is -OBs. In some ^{embodiments, R D4} 'is 2-nitrobenzene sulfonyloxy. In some ^{embodiments, R D4 'are, -OR D4a'} is. In some ^{embodiments, R D4} 'is -OMe. In some ^{embodiments, R D4} 'is _{-OCF 3.} In some ^{embodiments, R D4} 'is -OPh. In some ^{embodiments, R D4 'is, -OC (= O) R D4a} ' is. In some ^{embodiments, R D4} 'is -OC (= O) Me. In some ^{embodiments, R D4} 'is -OC (= O) CF _3. In some ^{embodiments, R D4} 'is -OC (= O) Ph. In some ^{embodiments, R D4} 'is -OC (= O) Cl. In some ^{embodiments, R D4 'is, -OC (= O) OR D4a} ' is. In some ^{embodiments, R D4} 'is -OC (= O) OMe. In some ^{embodiments, R D4} 'is -OC (= O) O (t -Bu).

In some embodiments, ^RD4a'is a substituted alkyl. In some embodiments, ^RD4a'is an unsubstituted alkyl. In some embodiments, ^RD4a'is C _1-6 alkyl. In some embodiments, ^RD4a'is methyl. In some embodiments, ^RD4a'is ethyl. In some embodiments, ^RD4a'is propyl. In some embodiments, ^RD4a'is butyl. In some embodiments, ^RD4a'is a substituted alkenyl. In some embodiments, ^RD4a'is an unsubstituted alkenyl. In some embodiments, ^RD4a'is vinyl. In some embodiments, ^RD4a'is a substituted alkynyl. In some embodiments, ^RD4a'is an unsubstituted alkynyl. In some embodiments, ^RD4a'is ethynyl. In some embodiments, ^RD4a'is a substituted carbocyclyl. In some embodiments, ^RD4a'is an unsubstituted carbocyclyl. In some embodiments, ^RD4a'is a substituted heterocyclyl. In some embodiments, ^RD4a'is an unsubstituted heterocyclyl. In some embodiments, ^RD4a'is a substituted aryl. In some embodiments, ^RD4a'is an unsubstituted aryl. In some embodiments, ^RD4a'is a substituted phenyl. In some embodiments, ^RD4a'is an unsubstituted phenyl. In some embodiments, ^RD4a'is a substituted heteroaryl. In some embodiments, ^RD4a'is an unsubstituted heteroaryl. In some embodiments, ^RD4a'is a substituted pyridyl. In some embodiments, ^RD4a'is an unsubstituted pyridyl.

In the compounds of formula (II), ^{R D} 'is a substituted group ^{R D5'} may contain. In some embodiments, ^RD5'is H. In some embodiments, ^RD5'is a substituted alkyl. In some embodiments, ^RD5'is an unsubstituted alkyl. In some embodiments, ^RD5'is C _1-6 alkyl. In some embodiments, ^RD5'is methyl. In some embodiments, ^RD5'is ethyl. In some embodiments, ^RD5'is propyl. In some embodiments, ^RD5'is butyl. In some embodiments, ^RD5'is a nitrogen protecting group. In some ^{embodiments, R D5} 'is Bn, BOC, Cbz, Fmoc, trifluoroacetyl, triphenylmethyl or Ts.

In some embodiments, R ^D1'and R ^D2'are hydrogen, respectively. In some embodiments, R ^D1'and R ^D3'are hydrogen, respectively. In some embodiments, R ^D2'and R ^D3'are hydrogen, respectively. In some embodiments, ^RD1 ', ^RD2 ', and ^RD3'are each hydrogen. In some embodiments, ^RD1 ', ^RD2 ', and ^RD3 ', and ^RD5'are hydrogen, respectively.

In some embodiments, a'is 1. In some embodiments, a'is 2.

In some embodiments, z'is 0. In some embodiments, z'is 1. In some embodiments, z'is 2. In some embodiments, z'is 3. In some embodiments, z'is 4. In some embodiments, z'is 5. In some embodiments, z'is 6.

In some embodiments, ^{Y Z} 'is -O-. In some embodiments, ^{Y Z} 'is = O. In some embodiments, ^{Y Z} 'is -S-. In some embodiments, Y ^Z'is = S. In some embodiments, ^{Y Z} 'is ^{-NR D6'} - a a, wherein ^{R D6} 'is _{hydrogen, C 1-6} alkyl or a nitrogen protecting group. In some embodiments, ^{Y Z} 'is -NH-. In some embodiments, ^{Y Z} 'is, -NCH ₃ - a. In some embodiments, ^{Y Z} 'are, -N (BOC) - a. In some embodiments, ^{Y Z} 'are, -N (Fmoc) - a. In some embodiments, ^{Y Z} 'are, -N (Cbz) - a. In some embodiments, ^{Y Z} 'are, -N (Bn) - a. In some embodiments, a ^{Y Z} 'is = ^{NR D6',} wherein ^{R D6} 'is _{hydrogen, C 1-6} alkyl or a nitrogen protecting group. In some embodiments, ^{Y Z} 'is = NH. In some embodiments, ^{Y Z} 'is = NCH _3. In some embodiments, ^{Y Z} 'is = NTs. In some embodiments, ^{Y Z} 'is = NBn. In some embodiments, ^{Y Z} 'is = NCH _{(Ph) 2.}

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のものである。 In some embodiments, ^{R D} 'has the formula:

belongs to. In some embodiments, ^{R D} 'has the formula:

belongs to. In some embodiments, ^{R D} 'has the formula:

belongs to. In some embodiments, ^{R D} 'has the formula:

belongs to. In some embodiments, ^{R D} 'has the formula:

belongs to. In some embodiments, ^{R D} 'has the formula:

belongs to. In some embodiments, ^{R D} 'has the formula:

belongs to. In some embodiments, ^{R D} 'has the formula:

belongs to. In some embodiments, ^{R D} 'has the formula:

belongs to. In some embodiments, ^{R D} 'has the formula:

belongs to. In some embodiments, ^{R D} 'has the formula:

belongs to. In some embodiments, ^{R D} 'has the formula:

belongs to. In some embodiments, ^{R D} 'has the formula:

belongs to. In some embodiments, ^{R D} 'has the formula:

belongs to. In some embodiments, ^{R D} 'has the formula:

belongs to. In some embodiments, ^{R D} 'has the formula:

belongs to. In some embodiments, ^{R D} 'has the formula:

belongs to. In some embodiments, ^{R D} 'has the formula:

belongs to. In some embodiments, ^{R D} 'has the formula:

belongs to. In some embodiments, ^{R D} 'has the formula:

belongs to. In some embodiments, ^{R D} 'has the formula:

belongs to. In some embodiments, ^{R D} 'has the formula:

belongs to. In some embodiments, ^{R D} 'has the formula:

belongs to. In some embodiments, ^{R D} 'has the formula:

belongs to. In some embodiments, ^{R D} 'has the formula:

belongs to. In some embodiments, ^{R D} 'has the formula:

belongs to.

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のものである。 Compounds of formula (II) or (V) includes a ^'aryl ring A which is substituted by a group' one or more R ^A optionally. In some embodiments, k'is 0. In some embodiments, the ring A'is the formula:

belongs to. In some embodiments, the ring A'is the formula:

belongs to. In some embodiments, k'is 1. In some embodiments, the ring A'is the formula:

belongs to. In some embodiments, the ring A'is the formula:

belongs to. In some embodiments, the ring A'is the formula:

belongs to. In some embodiments, the ring A'is the formula:

belongs to. In some embodiments, the ring A'is the formula:

belongs to. In some embodiments, the ring A'is the formula:

belongs to. In some embodiments, k'is 2. In some embodiments, the ring A'is the formula:

belongs to. In some embodiments, the ring A'is the formula:

belongs to. In some embodiments, the ring A'is the formula:

belongs to. In some embodiments, the ring A'is the formula:

belongs to. In some embodiments, the ring A'is the formula:

belongs to. In some embodiments, the ring A'is the formula:

belongs to. In some embodiments, the ring A'is the formula:

belongs to. In some embodiments, the ring A'is the formula:

belongs to. In some embodiments, the ring A'is the formula:

belongs to. In some embodiments, the ring A'is the formula:

belongs to. In some embodiments, k'is 3. In some embodiments, the ring A'is the formula:

belongs to. In some embodiments, the ring A'is the formula:

belongs to. In some embodiments, the ring A'is the formula:

belongs to. In some embodiments, the ring A'is the formula:

belongs to. In some embodiments, the ring A'is the formula:

belongs to. In some embodiments, k'is 4. In some embodiments, the ring A'is the formula:

belongs to. In some embodiments, the ring A'is the formula:

belongs to.

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のものである。ある態様において、ｋ’は、２である。ある態様において、環Ａ’は、式：

のものである。ある態様において、環Ａ’は、式：

のものである。ある態様において、環Ａ’は、式：

のものである。ある態様において、環Ａ’は、式：

のものである。ある態様において、環Ａ’は、式：

のものである。ある態様において、環Ａ’は、式：

のものである。ある態様において、環Ａ’は、式：

のものである。ある態様において、環Ａ’は、式：

のものである。 Compounds of formula (II) or (V) includes a ^'aryl ring A which is substituted by a group' one or more R ^A optionally. In some embodiments, X', Y'and Z'are bonds and Cy is hydrogen. In some embodiments, k'is 0. In some embodiments, the ring A'is the formula:

belongs to. In some embodiments, k'is 1. In some embodiments, the ring A'is the formula:

belongs to. In some embodiments, the ring A'is the formula:

belongs to. In some embodiments, the ring A'is the formula:

belongs to. In some embodiments, k'is 2. In some embodiments, the ring A'is the formula:

belongs to. In some embodiments, the ring A'is the formula:

belongs to. In some embodiments, the ring A'is the formula:

belongs to. In some embodiments, the ring A'is the formula:

belongs to. In some embodiments, the ring A'is the formula:

belongs to. In some embodiments, the ring A'is the formula:

belongs to. In some embodiments, the ring A'is the formula:

belongs to. In some embodiments, the ring A'is the formula:

belongs to.

である。ある態様において、少なくとも１個のＲ^Ａ’は、置換アリールである。ある態様において、少なくとも１個のＲ^Ａ’は、未置換アリールである。ある態様において、少なくとも１個のＲ^Ａ’は、置換フェニルである。ある態様において、少なくとも１個のＲ^Ａ’は、未置換フェニルである。ある態様において、少なくとも１個のＲ^Ａ’は、置換ヘテロアリールである。ある態様において、少なくとも１個のＲ^Ａ’は、未置換ヘテロアリールである。ある態様において、少なくとも１個のＲ^Ａ’は、置換ピリジルである。ある態様において、少なくとも１個のＲ^Ａ’は、未置換ピリジルである。ある態様において、少なくとも１個のＲ^Ａ’は、−ＯＲ^Ａ１’である。ある態様において、少なくとも１個のＲ^Ａ’は、−Ｏ（Ｃ_１−６アルキル）である。ある態様において、少なくとも１個のＲ^Ａ’は、−ＯＭｅである。ある態様において、少なくとも１個のＲ^Ａ’は、−ＯＨである。ある態様において、少なくとも１個のＲ^Ａ’は、−Ｎ（Ｒ^Ａ１’）_２である。ある態様において、少なくとも１個のＲ^Ａ’は、−ＮＨ_２である。ある態様において、少なくとも１個のＲ^Ａ’は、−ＳＲ^Ａ１’である。ある態様において、少なくとも１個のＲ^Ａ’は、−ＳＨである。ある態様において、少なくとも１個のＲ^Ａ’は、−ＮＲ^Ａ１’Ｃ（＝Ｏ）Ｎ（Ｒ^Ａ１’）_２である。ある態様において、少なくとも１個のＲ^Ａ’は、−ＮＨＣ（＝Ｏ）Ｎ（Ｒ^Ａ１’）_２である。ある態様において、少なくとも１個のＲ^Ａ’は、−ＮＨＣ（＝Ｏ）ＮＨＲ^Ａ１’である。ある態様において、少なくとも１個のＲ^Ａ’は、−ＮＨＣ（＝Ｏ）ＮＨ（Ｃ_１−６アルキル）である。ある態様において、少なくとも１個のＲ^Ａ’は、−ＮＨＣ（＝Ｏ）ＮＨＭｅである。ある態様において、少なくとも１個のＲ^Ａ’は、−ＮＨＣ（＝Ｏ）ＮＨ_２である。ある態様において、少なくとも１個のＲ^Ａ’は、−ＮＲ^Ａ１’Ｃ（＝Ｏ）ＮＨＲ^Ａ１’である。ある態様において、少なくとも１個のＲ^Ａ’は、−ＮＲ^Ａ１’Ｃ（＝Ｏ）ＮＨ_２である。ある態様において、少なくとも１個のＲ^Ａ’は、−ＮＲ^Ａ１’Ｓ（＝Ｏ）_２Ｒ^Ａ１’である。ある態様において、少なくとも１個のＲ^Ａ’は、−ＮＨＳ（＝Ｏ）_２Ｒ^Ａ１’である。ある態様において、少なくとも１個のＲ^Ａ’は、−ＮＨＳ（＝Ｏ）_２（Ｃ_１−６アルキル）である。ある態様において、少なくとも１個のＲ^Ａ’は、−ＮＨＳ（＝Ｏ）_２Ｍｅである。ある態様において、少なくとも１個のＲ^Ａ’は、−Ｓ（＝Ｏ）_２Ｎ（Ｒ^Ａ１’）_２である。ある態様において、少なくとも１個のＲ^Ａ’は、−Ｓ（＝Ｏ）_２Ｎ（Ｒ^Ａ１’）_２である。ある態様において、少なくとも１個のＲ^Ａ’は、−Ｓ（＝Ｏ）_２Ｎ（Ｃ_１−６アルキル）_２である。ある態様において、少なくとも１個のＲ^Ａ’は、−Ｓ（＝Ｏ）_２ＮＨ（Ｃ_１−６アルキル）である。ある態様において、少なくとも１個のＲ^Ａ’は、−Ｓ（＝Ｏ）_２ＮＨ（ｔ−Ｂｕ）である。ある態様において、少なくとも１個のＲ^Ａ’は、−Ｓ（＝Ｏ）_２ＮＨ_２である。 In the compound of formula (II) or (V), the ring A'may be substituted with ^{one or more RA' groups.} In certain embodiments, at least one of ^{R A} 'is H. In certain embodiments, at least two R ^{A 'group} is H. In certain embodiments, at least three R ^{A 'group} is H. In certain embodiments, at least four R ^{A 'group} is H. In certain embodiments, at least one of R ^{A 'is} halogen. In certain embodiments, at least one of ^{R A} 'is F. In certain embodiments, at least one of ^{R A} 'is is Cl. In certain embodiments, at least one of ^{R A} 'is Br. In certain embodiments, at least one of ^{R A} 'is I (iodine). In some embodiments, ^'at least one of R ^A, a substituted acyl. In certain embodiments, at least one of ^{R A 'is, -C (= O) N (} R A1') _2. In certain embodiments, at least one of ^{R A 'is, -C (= O) NHR A1} ' is. In certain embodiments, at least one of ^{R A} 'is _{-C (= O) NH (C} 1-6 alkyl). In certain embodiments, at least one of ^{R A} 'is -C (= O) NHMe. In certain embodiments, at least one of ^{R A} 'is -C (= O) NH _2. In certain embodiments, at least one of R ^{A 'is} unsubstituted acyl. In certain embodiments, at least one of R ^{A 'is} acetyl. In some embodiments, ^'at least one of R ^A, is a substituted alkyl. In certain embodiments, at least one of R ^{A 'is} a substituted methyl. In certain embodiments, at least one of R ^{A 'is} unsubstituted alkyl. In certain embodiments, at least one of ^{R A} _'is a _{C 1-6} alkyl. In certain embodiments, at least one of R ^{A 'is} methyl. In certain embodiments, at least one of R ^{A 'is} ethyl. In certain embodiments, at least one of R ^{A 'is} propyl. In certain embodiments, at least one of R ^{A 'is} butyl. In some embodiments, ^'at least one of R ^A, a substituted alkenyl. In certain embodiments, at least one of R ^{A 'is} unsubstituted alkenyl. In some embodiments, ^'at least one of R ^A, is substituted alkynyl. In certain embodiments, at least one of R ^{A 'is} unsubstituted alkynyl. In some embodiments, ^'at least one of R ^A, is a substituted carbocyclyl. In certain embodiments, at least one of R ^{A 'is} unsubstituted carbocyclyl. In some embodiments, ^'at least one of R ^A, is a substituted heterocyclyl. In certain embodiments, at least one of R ^{A 'is} unsubstituted heterocyclyl. In some embodiments, 'at least one of ^{R A,}

Is. In some embodiments, 'at least one of R A, is a substituted aryl. In certain embodiments, at least one of R A 'is unsubstituted aryl. In some embodiments, 'at least one of R A, is a substituted phenyl. In certain embodiments, at least one of R A 'is unsubstituted phenyl. In some embodiments, 'at least one of R A, is substituted heteroaryl. In certain embodiments, at least one of R A 'is unsubstituted heteroaryl. In some embodiments, 'at least one of R A, is a substituted pyridyl. In certain embodiments, at least one of R A 'is unsubstituted pyridyl. In certain embodiments, at least one of R A 'is, -OR A1' is. In certain embodiments, at least one of R A 'is -O (C 1-6 alkyl). In some embodiments, 'at least one of R A, is -OMe. In certain embodiments, at least one of R A 'is -OH. In certain embodiments, at least one of R A 'is, -N (R A1') 2. In certain embodiments, at least one of R A 'is -NH 2. In certain embodiments, at least one of R A 'is, -SR A1' is. In certain embodiments, at least one of R A 'is -SH. In certain embodiments, at least one of R A 'is, -NR A1' C (= O ) N (R A1 ') 2. In certain embodiments, at least one of R A 'is, -NHC (= O) N ( R A1') 2. In certain embodiments, at least one of R A 'is, -NHC (= O) NHR A1 ' is. In certain embodiments, at least one of R A 'is -NHC (= O) NH (C 1-6 alkyl). In certain embodiments, at least one of R A 'is -NHC (= O) NHMe. In certain embodiments, at least one of R A 'is -NHC (= O) NH 2. In certain embodiments, at least one of R A 'is, -NR A1' is a C (= O) NHR A1 ' . In certain embodiments, at least one of R A 'is, -NR A1' is a C (= O) NH 2. In certain embodiments, at least one of R A 'is, -NR A1' is S (= O) 2 R A1 '. In certain embodiments, at least one of R A 'is, -NHS (= O) 2 R A1' is. In certain embodiments, at least one of R A 'is -NHS (= O) 2 (C 1-6 alkyl). In certain embodiments, at least one of R A 'is -NHS (= O) 2 Me. In certain embodiments, at least one of R A 'is, -S (= O) 2 N (R A1') 2. In certain embodiments, at least one of R A 'is, -S (= O) 2 N (R A1') 2. In certain embodiments, at least one of R A 'is, -S (= O) 2 N (C 1-6 alkyl) 2. In certain embodiments, at least one of R A 'is -S (= O) 2 NH ( C 1-6 alkyl). In certain embodiments, at least one of R A 'is -S (= O) 2 NH ( t-Bu). In certain embodiments, at least one of R A 'is -S (= O) 2 NH 2 .

である。ある態様において、少なくとも１個のＲ^Ｂ’は、

である。ある態様において、少なくとも１個のＲ^Ｂ’は、

である。ある態様において、少なくとも１個のＲ^Ｂ’は、

である。ある態様において、少なくとも１個のＲ^Ｂ’は、

である。ある態様において、少なくとも１個のＲ^Ｂ’は、

である。ある態様において、少なくとも１個のＲ^Ｂ’は、

である。ある態様において、少なくとも１個のＲ^Ｂ’は、

である。ある態様において、少なくとも１個のＲ^Ｂ’は、

である。ある態様において、少なくとも１個のＲ^Ｂ’は、

である。ある態様において、少なくとも１個のＲ^Ｂ’は、

である。ある態様において、少なくとも１個のＲ^Ｂ’は、

である。ある態様において、少なくとも１個のＲ^Ｂ’は、

である。ある態様において、少なくとも１個のＲ^Ｂ’は、

である。ある態様において、少なくとも１個のＲ^Ｂ’は、

である。ある態様において、少なくとも１個のＲ^Ｂ’は、

である。ある態様において、少なくとも１個のＲ^Ｂ’は、

である。ある態様において、少なくとも１個のＲ^Ｂ’は、

である。ある態様において、少なくとも１個のＲ^Ｂ’は、

である。ある態様において、少なくとも１個のＲ^Ｂ’は、

である。ある態様において、少なくとも１個のＲ^Ｂ’は、

である。ある態様において、少なくとも１個のＲ^Ｂ’は、

である。ある態様において、少なくとも１個のＲ^Ｂ’は、

である。ある態様において、少なくとも１個のＲ^Ｂ’は、

である。ある態様において、少なくとも１個のＲ^Ｂ’は、

である。ある態様において、少なくとも１個のＲ^Ｂ’は、

である。ある態様において、少なくとも１個のＲ^Ｂ’は、

である。ある態様において、少なくとも１個のＲ^Ｂ’は、

である。ある態様において、少なくとも１個のＲ^Ｂ’は、

である。ある態様において、少なくとも１個のＲ^Ｂ’は、

である。ある態様において、少なくとも１個のＲ^Ｂ’は、

である。ある態様において、少なくとも１個のＲ^Ｂ’は、

である。ある態様において、少なくとも１個のＲ^Ｂ’は、

である。ある態様において、少なくとも１個のＲ^Ｂ’は、

である。ある態様において、少なくとも１個のＲ^Ｂ’は、

である。ある態様において、少なくとも１個のＲ^Ｂ’は、

である。ある態様において、少なくとも１個のＲ^Ｂ’は、

である。ある態様において、少なくとも１個のＲ^Ｂ’は、

である。ある態様において、少なくとも１個のＲ^Ｂ’は、

である。ある態様において、少なくとも１個のＲ^Ｂ’は、

である。ある態様において、少なくとも１個のＲ^Ｂ’は、

である。 In the compounds of formula (II) or (V), the ring C 'is one or two or more R B' may be substituted with a group. In certain embodiments, at least one of R B 'is H. In certain embodiments, at least two R B 'groups are H. In some embodiments, at least three of R B 'groups are H. In certain embodiments, at least four R B 'groups are H. In certain embodiments, at least one of R B 'is halogen. In certain embodiments, at least one of R B 'is F. In certain embodiments, at least one of R B 'is is Cl. In certain embodiments, at least one of R B 'is Br. In certain embodiments, at least one of R B 'is I (iodine). In some embodiments, 'at least one of R B, is a substituted acyl. In certain embodiments, at least one of R B 'is, -C (= O) N ( R A1') 2. In certain embodiments, at least one of R B 'is, -C (= O) NHR A1 ' is. In certain embodiments, at least one of R B 'is -C (= O) NH (C 1-6 alkyl). In certain embodiments, at least one of R B 'is -C (= O) NHMe. In certain embodiments, at least one of R B 'is -C (= O) NH 2. In certain embodiments, at least one of R B 'is an unsubstituted acyl. In certain embodiments, at least one of R B 'is acetyl. In some embodiments, 'at least one of R B, is a substituted alkyl. In some embodiments, 'at least one of R B, is substituted methyl. In certain embodiments, at least one of R B 'is an unsubstituted alkyl. In certain embodiments, at least one of R B 'is C 1-6 alkyl. In certain embodiments, at least one of R B 'is methyl. In certain embodiments, at least one of R B 'is ethyl. In certain embodiments, at least one of R B 'is propyl. In certain embodiments, at least one of R B 'is butyl. In some embodiments, 'at least one of R B, is a -CF 3. In some embodiments, 'at least one of R B, is substituted alkenyl. In certain embodiments, at least one of R B 'is an unsubstituted alkenyl. In some embodiments, 'at least one of R B, is substituted alkynyl. In certain embodiments, at least one of R B 'is an unsubstituted alkynyl. In some embodiments, 'at least one of R B, is a substituted carbocyclyl. In certain embodiments, at least one of R B 'is an unsubstituted carbocyclyl. In some embodiments, 'at least one of R B, is a substituted heterocyclyl. In certain embodiments, at least one of R B 'is an unsubstituted heterocyclyl. In some embodiments, 'at least one of R B, is a substituted aryl. In certain embodiments, at least one of R B 'is an unsubstituted aryl. In some embodiments, 'at least one of R B, is a substituted phenyl. In certain embodiments, at least one of R B 'is an unsubstituted phenyl. In some embodiments, 'at least one of R B, is substituted heteroaryl. In certain embodiments, at least one of R B 'is an unsubstituted heteroaryl. In some embodiments, 'at least one of R B, is a substituted pyridyl. In certain embodiments, at least one of R B 'is an unsubstituted pyridyl. In certain embodiments, at least one of R B 'is -O A1. In certain embodiments, at least one of R B 'is -O (C 1-6 alkyl). In certain embodiments, at least one of R B 'is -OMe. In certain embodiments, at least one of R B 'is -OH. In certain embodiments, at least one of R B 'is, -N (R A1') 2. In certain embodiments, at least one of R B 'is -NH 2. In certain embodiments, at least one of R B 'is, -SR A1' is. In certain embodiments, at least one of R B 'is -SH. In certain embodiments, at least one of R B 'is, -NR A1' C (= O ) N (R A1 ') 2. In certain embodiments, at least one of R B 'is, -NHC (= O) N ( R A1') 2. In certain embodiments, at least one of R B 'is, -NHC (= O) NHR A1 ' is. In certain embodiments, at least one of R B 'is -NHC (= O) NH (C 1-6 alkyl). In certain embodiments, at least one of R B 'is -NHC (= O) NHMe. In certain embodiments, at least one of R B 'is -NHC (= O) NH 2. In some embodiments, 'the, -NR A1' at least one of R B is C (= O) NHR A1 ' . In some embodiments, 'the, -NR A1' at least one of R B is C (= O) NH 2. In certain embodiments, at least one of R B 'is, -NR A1' is S (= O) 2 R A1 '. In certain embodiments, at least one of R B 'is, -NHS (= O) 2 R A1' is. In certain embodiments, at least one of R B 'is -NHS (= O) 2 (C 1-6 alkyl). In certain embodiments, at least one of R B 'is -NHS (= O) 2 Me. In certain embodiments, at least one of R B 'is, -S (= O) 2 N (R A1') 2. In certain embodiments, at least one of R B 'is, -S (= O) 2 N (R A1') 2. In certain embodiments, at least one of R B 'is -S (= O) 2 N ( C 1-6 alkyl) 2. In certain embodiments, at least one of R B 'is -S (= O) 2 NH ( C 1-6 alkyl). In certain embodiments, at least one of R B 'is -S (= O) 2 NH ( t-Bu). In certain embodiments, at least one of R B 'is -S (= O) 2 NH 2 . In some embodiments, 'at least one of R B, is a substituted imidazole. In certain embodiments, at least one of R B 'is a substituted piperidine (piperidine). In certain embodiments, at least one of R B 'is a substituted piperidine (piperizine). In some embodiments, 'at least one of R B, is a substituted pyrrolidine. In some embodiments, 'at least one of R B, is a substituted morpholine. In some embodiments, 'at least one of R B, is substituted Jiazapan. In certain embodiments, at least one of R B 'is

Is. In certain embodiments, at least one of ^{R B} 'is

Is. In certain embodiments, at least one of ^{R B} 'is

Is. In certain embodiments, at least one of ^{R B} 'is

Is. In certain embodiments, at least one of ^{R B} 'is

Is. In certain embodiments, at least one of ^{R B} 'is

Is. In certain embodiments, at least one of ^{R B} 'is

Is. In certain embodiments, at least one of ^{R B} 'is

Is. In certain embodiments, at least one of ^{R B} 'is

Is. In certain embodiments, at least one of ^{R B} 'is

Is. In certain embodiments, at least one of ^{R B} 'is

Is. In certain embodiments, at least one of ^{R B} 'is

Is. In certain embodiments, at least one of ^{R B} 'is

Is. In certain embodiments, at least one of ^{R B} 'is

Is. In certain embodiments, at least one of ^{R B} 'is

Is. In certain embodiments, at least one of ^{R B} 'is

Is. In certain embodiments, at least one of ^{R B} 'is

Is. In certain embodiments, at least one of ^{R B} 'is

Is. In certain embodiments, at least one of ^{R B} 'is

Is. In certain embodiments, at least one of ^{R B} 'is

Is. In certain embodiments, at least one of ^{R B} 'is

Is. In certain embodiments, at least one of ^{R B} 'is

Is. In certain embodiments, at least one of ^{R B} 'is

Is. In certain embodiments, at least one of ^{R B} 'is

Is. In certain embodiments, at least one of ^{R B} 'is

Is. In certain embodiments, at least one of ^{R B} 'is

Is. In certain embodiments, at least one of ^{R B} 'is

Is. In certain embodiments, at least one of ^{R B} 'is

Is. In certain embodiments, at least one of ^{R B} 'is

Is. In certain embodiments, at least one of ^{R B} 'is

Is. In certain embodiments, at least one of ^{R B} 'is

Is. In certain embodiments, at least one of ^{R B} 'is

Is. In certain embodiments, at least one of ^{R B} 'is

Is. In certain embodiments, at least one of ^{R B} 'is

Is. In certain embodiments, at least one of ^{R B} 'is

Is. In certain embodiments, at least one of ^{R B} 'is

Is. In certain embodiments, at least one of ^{R B} 'is

Is. In certain embodiments, at least one of ^{R B} 'is

Is. In certain embodiments, at least one of ^{R B} 'is

Is. In certain embodiments, at least one of ^{R B} 'is

Is. In certain embodiments, at least one of ^{R B} 'is

Is.

In some embodiments, two R ^{B 'groups} form a linked with 1,3-dioxolane. In some embodiments, two R ^{B 'groups} are linked, the aryl ring C' to form a fused 1,3 dioxolane, including benzodioxolane optionally substituted with. In some embodiments, two ^{R B} 'groups form a linked 1,2,3-thiadiazole. In some embodiments, two R ^{B 'groups} are linked, the aryl ring C' to form a fused 1,2,3-thiadiazole in, together, an optionally substituted benzo [d] [1, 2,3] Contains thiadiazole.

In certain embodiments, at least one of ^{R A1} 'is H. In some embodiments, ^'at least one of R ^A1, substituted acyl. In certain embodiments, at least one of R ^{A1 'is} a non-substituted acyl. In certain embodiments, at least one of ^{R A1} 'is acetyl. In certain embodiments, at least one of R ^{A1 'is} substituted alkyl. In certain embodiments, at least one of R ^{A1 'is} unsubstituted alkyl. In certain embodiments, at least one of ^{R A1} _'is a _{C 1-6} alkyl. In certain embodiments, at least one of ^{R A1} 'is methyl. In certain embodiments, at least one of ^{R A1} 'is ethyl. In certain embodiments, at least one of ^{R A1} 'is propyl. In certain embodiments, at least one of ^{R A1} 'is butyl. In some embodiments, ^'at least one of R ^A1, is substituted alkenyl. In certain embodiments, at least one of R ^{A1 'is} a non-substituted alkenyl. In some embodiments, ^'at least one of R ^A1, is substituted alkynyl. In certain embodiments, at least one of R ^{A1 'is} a non-substituted alkynyl. In some embodiments, ^'at least one of R ^A1, substituted carbocyclyl. In certain embodiments, at least one of R ^{A1 'is} unsubstituted carbocyclyl. In some embodiments, ^'at least one of R ^A1, substituted heterocyclyl. In certain embodiments, at least one of R ^{A1 'is} unsubstituted heterocyclyl. In some embodiments, ^'at least one of R ^A1, substituted aryl. In certain embodiments, at least one of R ^{A1 'is} an unsubstituted aryl. In some embodiments, ^'at least one of R ^A1, is substituted phenyl. In certain embodiments, at least one of R ^{A1 'is} an unsubstituted phenyl. In some embodiments, ^'at least one of R ^A1, is substituted heteroaryl. In certain embodiments, at least one of R ^{A1 'is} unsubstituted heteroaryl. In some embodiments, ^'at least one of R ^A1, is substituted pyridyl. In certain embodiments, at least one of R ^{A1 'is} an unsubstituted pyridyl. In some embodiments, ^'at least one of R ^A1, when attached to the nitrogen atom is a nitrogen protecting group. In some embodiments, 'at least one of ^{R A1,} when attached to a nitrogen atom, Bn, BOC, Cbz, Fmoc, trifluoroacetyl, triphenylmethyl or Ts. In some embodiments, ^RA1'is an oxygen protecting group when attached to an oxygen atom. In some ^{embodiments, R A1} ', if attached to an oxygen atom, is silyl, TBDPS, TBDMS, TIPS, TES , TMS, MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl or benzoyl .. In some embodiments, ^RA1'is a sulfur protecting group if it is attached to a sulfur atom. In some ^{embodiments, R A1} ', if attached to the sulfur atom, acetamidomethyl, t-Bu, 3- nitro-2-pyridine sulfenyl, 2-pyridine - a sulfenyl or triphenylmethyl.

In the compounds of formula (II) or (V), 2 pieces of R ^{A1 'group} is coupled, optionally substituted carbocyclic ring, heterocyclic ring optionally substituted, any substituted aryl, Alternatively, an arbitrarily substituted heteroaryl ring may be formed. In some embodiments, two R ^{A1 'groups} are linked to form a carbocyclic ring. In some embodiments, two R ^{A1 'groups} are linked to form an unsubstituted carbocyclic ring. In some embodiments, two R ^{A1 'groups} are linked to form a substituted heterocyclic ring. In some embodiments, two R ^{A1 'group} forms a heterocyclic ring unsubstituted coupled. In some embodiments, two R ^{A1 'groups} are linked to form a substituted aryl ring. In some embodiments, two R ^{A1 'groups} form an unsubstituted aryl ring is connected. In some embodiments, two R ^{A1 'groups} are linked to form a substituted phenyl ring. In some embodiments, two R ^{A1 'groups} form an unsubstituted phenyl ring linked. In some embodiments, two R ^{A1 'groups} are linked to form a substituted heteroaryl ring. In some embodiments, two R ^{A1 'group} forms a unsubstituted heteroaryl ring is connected.

In some embodiments, ^{R A} 'is ^{-OR A1'} is, k 'is 1. In some embodiments, ^{R A} 'is -O _{(C 1-6} alkyl), k' is 1. In some embodiments, ^{R A} 'is -OMe, k' is 1. In some embodiments, ^{R A} 'is -OH, k' is 1.

In some embodiments, ^{R A} 'is a substituted _{C 1-6} alkyl; k' is 1. In some embodiments, ^{R A} 'is an unsubstituted _{C 1-6} alkyl; k' is 1. In some embodiments, R A ^'is methyl; k' is 1. In some embodiments, ^{R A} 'is an -CF _3; k' is 1. In some embodiments, R A ^'is ethyl; k' is 1. In some embodiments, ^RA is propyl; k'is 1. In some embodiments, R A ^'is butyl; k' is 1. In some embodiments, R A ^'is propyl; k' is 1. In some embodiments, R A ^'is butyl; k' is 1. In some embodiments, R A ^'is propyl; k' is 1. In some embodiments, R A ^'is butyl; k' is 1.

In some embodiments, R A ^'is a halogen; k' is 1. In some embodiments, ^{R A} 'is an F; k' is 1. In some embodiments, ^{R A} 'is an Cl; k' is 1. In some embodiments, ^{R A} 'is an Br; k' is 1. In some embodiments, ^{R A} 'is an I (iodine); k' is 1.

In certain embodiments, one of ^{R A} 'is halogen, another ^{R A'} is a substituted _{C 1-6} alkyl; k 'is 2. In certain embodiments, one of ^{R A} 'is F, another ^{R A'} is a substituted _{C 1-6} alkyl; k 'is 2. In certain embodiments, one of ^{R A} 'are Cl, another ^{R A'} is a substituted _{C 1-6} alkyl; k 'is 2. In certain embodiments, one of ^{R A} 'is halogen, another ^{R A'} is an unsubstituted _{C 1-6} alkyl; k 'is 2. In certain embodiments, one of ^{R A} 'is F, another ^{R A'} is an unsubstituted _{C 1-6} alkyl; k 'is 2. In certain embodiments, one of ^{R A} 'are Cl, another ^{R A'} is an unsubstituted _{C 1-6} alkyl; k 'is 2. In certain embodiments, one of R ^{A 'is} halogen, another R ^A' is methyl; k 'is 2. In certain embodiments, one of R ^{A 'is} F, another R ^A' is methyl; k 'is 2. In certain embodiments, one of R ^{A 'are} Cl, another R ^A' is methyl; k 'is 2. In certain embodiments, one of ^{R A} 'is halogen, another ^{R A'} is an -CF _3; k 'is 2. In certain embodiments, one of ^{R A} 'is F, another ^{R A'} is an -CF _3; k 'is 2. In certain embodiments, one of ^{R A} 'are Cl, another ^{R A'} is an -CF _3; k 'is 2.

In the compounds of formula (II) or (V), the linkers X', Y'and Z'are divalent linker moieties. In some embodiments, X'is a bond. In some embodiments, X'is a single bond. In some embodiments, X'is -CH ₂ . In some embodiments, X'is -CHR ^A '. In some embodiments, X'is -CH. In some embodiments, X'is -C ( ^RA ') ₂ . In some embodiments, X'is -C. In some embodiments, X'is -N. In some embodiments, X'is -NR ^A '. In some embodiments, X'is -O. In some embodiments, X'is −C = O. In some embodiments, X'is -O. In some embodiments, X'is -S. In some embodiments, X 'is optionally, R ^A' may form a ring of 5-8 members with or R ^{B '.} In some embodiments, Y'is a bond. In some embodiments, Y'is a single bond. In some embodiments, Y'is -CH ₂ . In some embodiments, Y'is -CHR ^A '. In some embodiments, Y'is -CH. In some embodiments, Y'is -C ( ^RA ') ₂ . In some embodiments, Y'is -C. In some embodiments, Y'is -N. In some embodiments, Y'is -NR ^A '. In some embodiments, Y'is −O. In some embodiments, Y'is −C = O. In some embodiments, Y'is -S. In certain embodiments, Y 'is optionally, R ^A' may form a ring of 5-8 members with or R ^{B '.} In some embodiments, Z'is a bond. In some embodiments, Z'is a single bond. In some embodiments, Z'is -CH ₂ . In some embodiments, Z'is -CHR ^A '. In some embodiments, Z'is -CH. In some embodiments, Z'is -C ( ^RA ') ₂ . In some embodiments, Z'is -C. In some embodiments, Z'is -N. In some embodiments, Z'is -NR ^A '. In some embodiments, Z'is -O. In some embodiments, Z'is -C = O. In some embodiments, Z'is -S. In some embodiments, Z 'is optionally, R ^A' may form a ring of 5-8 members with or R ^{B '.}

を表す。ある態様において、Ｘ’、Ｙ’およびＺ’は、一緒に、

を表す。ある態様において、Ｘ’、Ｙ’およびＺ’は、一緒に、

を表す。ある態様において、Ｘ’、Ｙ’およびＺ’は、一緒に、

を表す。ある態様において、Ｘ’、Ｙ’およびＺ’は、一緒に、

を表す。ある態様において、Ｘ’、Ｙ’およびＺ’は、一緒に、

を表す。ある態様において、Ｘ’、Ｙ’およびＺ’は、一緒に、

を表す。ある態様において、Ｘ’、Ｙ’およびＺ’は、一緒に、

を表す。ある態様において、Ｘ’、Ｙ’およびＺ’は、一緒に、

を表す。ある態様において、Ｘ’、Ｙ’およびＺ’は、一緒に、

を表す。ある態様において、Ｘ’、Ｙ’およびＺ’は、一緒に、

を表す。ある態様において、Ｘ’、Ｙ’およびＺ’は、一緒に、

を表す。ある態様において、Ｘ’、Ｙ’およびＺ’は、一緒に、

を表す。ある態様において、Ｘ’、Ｙ’およびＺ’は、一緒に、

を表す。ある態様において、Ｘ’、Ｙ’およびＺ’は、一緒に、

を表す。ある態様において、Ｘ’、Ｙ’およびＺ’は、一緒に、

を表す。ある態様において、Ｘ’、Ｙ’およびＺ’は、一緒に、

を表す。ある態様において、Ｘ’、Ｙ’およびＺ’は、一緒に、

を表す。ある態様において、Ｘ’、Ｙ’およびＺ’は、一緒に、

を表す。ある態様において、Ｘ’、Ｙ’およびＺ’は、一緒に、

を表す。ある態様において、Ｘ’、Ｙ’およびＺ’は、一緒に、

を表す。ある態様において、Ｘ’、Ｙ’およびＺ’は、一緒に、

を表す。ある態様において、Ｘ’、Ｙ’およびＺ’は、一緒に、

を表す。ある態様において、Ｘ’、Ｙ’およびＺ’は、一緒に、

を表す。ある態様において、Ｘ’、Ｙ’およびＺ’は、一緒に、

を表す。ある態様において、Ｘ’、Ｙ’およびＺ’は、一緒に、

を表す。ある態様において、Ｘ’、Ｙ’およびＺ’は、一緒に、

を表す。ある態様において、Ｘ’、Ｙ’およびＺ’は、一緒に、

を表す。ある態様において、Ｘ’、Ｙ’およびＺ’は、一緒に、

を表す。ある態様において、Ｘ’、Ｙ’およびＺ’は、一緒に、

を表す。ある態様において、Ｘ’、Ｙ’およびＺ’は、一緒に、

を表す。ある態様において、Ｘ’、Ｙ’およびＺ’は、一緒に、

を表す。ある態様において、Ｘ’、Ｙ’およびＺ’は、一緒に、

を表す。ある態様において、Ｘ’、Ｙ’およびＺ’は、一緒に、

を表す。ある態様において、Ｘ’、Ｙ’およびＺ’は、一緒に、

を表す。ある態様において、Ｘ’、Ｙ’およびＺ’は、一緒に、

を表す。ある態様において、Ｘ’、Ｙ’およびＺ’は、一緒に、単結合を表す。 In compounds of formula (II) or (V), linkers X', Y'and Z'may be combined to represent a particular linking group. In some embodiments, the X', Y'and Z'are together,

Represents. In some embodiments, the X', Y'and Z'are together,

Represents. In some embodiments, the X', Y'and Z'are together,

Represents. In some embodiments, the X', Y'and Z'are together,

Represents. In some embodiments, the X', Y'and Z'are together,

Represents. In some embodiments, the X', Y'and Z'are together,

Represents. In some embodiments, the X', Y'and Z'are together,

Represents. In some embodiments, the X', Y'and Z'are together,

Represents. In some embodiments, the X', Y'and Z'are together,

Represents. In some embodiments, the X', Y'and Z'are together,

Represents. In some embodiments, the X', Y'and Z'are together,

Represents. In some embodiments, the X', Y'and Z'are together,

Represents. In some embodiments, the X', Y'and Z'are together,

Represents. In some embodiments, the X', Y'and Z'are together,

Represents. In some embodiments, the X', Y'and Z'are together,

Represents. In some embodiments, the X', Y'and Z'are together,

Represents. In some embodiments, the X', Y'and Z'are together,

Represents. In some embodiments, the X', Y'and Z'are together,

Represents. In some embodiments, the X', Y'and Z'are together,

Represents. In some embodiments, the X', Y'and Z'are together,

Represents. In some embodiments, the X', Y'and Z'are together,

Represents. In some embodiments, the X', Y'and Z'are together,

Represents. In some embodiments, the X', Y'and Z'are together,

Represents. In some embodiments, the X', Y'and Z'are together,

Represents. In some embodiments, the X', Y'and Z'are together,

Represents. In some embodiments, the X', Y'and Z'are together,

Represents. In some embodiments, the X', Y'and Z'are together,

Represents. In some embodiments, the X', Y'and Z'are together,

Represents. In some embodiments, the X', Y'and Z'are together,

Represents. In some embodiments, the X', Y'and Z'are together,

Represents. In some embodiments, the X', Y'and Z'are together,

Represents. In some embodiments, the X', Y'and Z'are together,

Represents. In some embodiments, the X', Y'and Z'are together,

Represents. In some embodiments, the X', Y'and Z'are together,

Represents. In some embodiments, the X', Y'and Z'are together,

Represents. In some embodiments, the X', Y'and Z'are together,

Represents. In some embodiments, X', Y'and Z'together represent a single bond.

In the compounds of formula (II) or (V), the linkers Q'and U'are divalent linker moieties. In some embodiments, Q'is -NR ^A '. In some embodiments, Q'is -NH. In some embodiments, Q'is −C = O. In some embodiments, Q 'is, -NR ^A' is CO. In some embodiments, Q'is a bond. In some embodiments, X 'is optionally, R ^A' may form a ring of 5-8 members with or R ^{B '.} In some embodiments, U'is -NR ^A '. In some embodiments, U'is -NH. In some embodiments, U'is -C = O. In some embodiments, U 'is, -NR ^A' is CO. In some embodiments, U'is a bond. In some embodiments, U 'is optionally, R ^A' may form a ring of 5-8 members with or R ^{B '.}

を表す。ある態様において、Ｑ’およびＵ’は、一緒に、

を表す。ある態様において、Ｑ’およびＵ’は、一緒に、

を表す。ある態様において、Ｑ’およびＵ’は、一緒に、

を表す。ある態様において、Ｑ’およびＵ’は、一緒に、

を表す。ある態様において、Ｑ’およびＵ’は、一緒に、

を表す。ある態様において、Ｑ’およびＵ’は、一緒に、

を表す。ある態様において、Ｑ’およびＵ’は、一緒に、

を表す。ある態様において、Ｑ’およびＵ’は、一緒に、

を表す。ある態様において、Ｑ’およびＵ’は、一緒に、

を表す。ある態様において、Ｑ’およびＵ’は、一緒に、

を表す。ある態様において、Ｑ’およびＵ’は、一緒に、

を表す。 In compounds of formula (II) or (V), the linkers Q'and U'may be combined to represent a particular linking group. In some embodiments, Q'and U'are together,

Represents. In some embodiments, Q'and U'are together,

Represents. In some embodiments, Q'and U'are together,

Represents. In some embodiments, Q'and U'are together,

Represents. In some embodiments, Q'and U'are together,

Represents. In some embodiments, Q'and U'are together,

Represents. In some embodiments, Q'and U'are together,

Represents. In some embodiments, Q'and U'are together,

Represents. In some embodiments, Q'and U'are together,

Represents. In some embodiments, Q'and U'are together,

Represents. In some embodiments, Q'and U'are together,

Represents. In some embodiments, Q'and U'are together,

Represents.

Cy of formula (II) or (V) may be an arbitrarily substituted aryl ring. In some embodiments, the ring Cy is a substituted aryl ring. In some embodiments, Cy is an unsubstituted aryl ring. In some embodiments, Cy is a monocyclic aryl ring. In some embodiments, Cy is a substituted phenyl. In some embodiments, Cy is an unsubstituted phenyl. In some embodiments, Cy is a bicyclic aryl ring. In some embodiments, Cy is a substituted naphthyl. In some embodiments, Cy is an unsubstituted naphthyl. In some embodiments, Cy is fused with one or more optionally substituted carbocyclic groups, optionally substituted heterocyclic groups, optionally substituted aryl groups, or optionally substituted heteroaryl groups. , Arbitrarily substituted aryl ring, wherein the bonding point is on the aryl ring.

であって、ここでＸ’は、任意の自由に原子価が合う位置に連結されてよい。ある態様において、Ｃｙは、

であって、ここでＸ’は、任意の自由に原子価が合う位置に連結されてよい。ある態様において、Ｃｙは、

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であって、ここでＸ’は、任意の自由に原子価が合う位置に連結されてよい。ある態様において、Ｃｙは、

であって、ここでＸ’は、任意の自由に原子価が合う位置に連結されてよい。ある態様において、Ｃｙは、

であって、ここでＸ’は、任意の自由に原子価が合う位置に連結されてよい。ある態様において、Ｃｙは、

であって、ここでＸ’は、任意の自由に原子価が合う位置に連結されてよい。ある態様において、Ｃｙは、

であって、ここでＸ’は、任意の自由に原子価が合う位置に連結されてよい。ある態様において、Ｃｙは、

であって、ここでＸ’は、任意の自由に原子価が合う位置に連結されてよい。ある態様において、Ｃｙは、

であって、ここでＸ’は、任意の自由に原子価が合う位置に連結されてよい。ある態様において、Ｃｙは、

であって、ここでＸ’は、任意の自由に原子価が合う位置に連結されてよい。ある態様において、Ｃｙは、

であって、ここでＸ’は、任意の自由に原子価が合う位置に連結されてよい。ある態様において、Ｃｙは、

であって、ここでＸ’は、任意の自由に原子価が合う位置に連結されてよい。ある態様において、Ｃｙは、

であって、ここでＸ’は、任意の自由に原子価が合う位置に連結されてよい。ある態様において、Ｃｙは、

であって、ここでＸ’は、任意の自由に原子価が合う位置に連結されてよい。ある態様において、Ｃｙは、

であって、ここでＸ’は、任意の自由に原子価が合う位置に連結されてよい。ある態様において、Ｃｙは、

であって、ここでＸ’は、任意の自由に原子価が合う位置に連結されてよい。 Cy of formula (II) or (V) may also be an arbitrarily substituted heteroaryl ring. In some embodiments, Cy is a substituted heteroaryl ring. In some embodiments, Cy is an unsubstituted heteroaryl ring. In some embodiments, Cy is a monocyclic heteroaryl ring. In some embodiments, Cy is a 5-membered monocyclic heteroaryl ring. In some embodiments, Cy is a 5-membered monocyclic heteroaryl ring having one heteroatom selected from the group consisting of S, N and O. In some embodiments, Cy is a 5-membered monocyclic heteroaryl ring having two heteroatoms selected from the group consisting of S, N and O. In some embodiments, Cy is a 5-membered monocyclic heteroaryl ring having 3 heteroatoms selected from the group consisting of S, N and O. In some embodiments, Cy is a substituted pyrrolyl. In some embodiments, Cy is an unsubstituted pyrrolyl. In some embodiments, Cy is a substituted flanyl. In some embodiments, Cy is an unsubstituted flanyl. In some embodiments, Cy is a substituted thienyl. In some embodiments, Cy is an unsubstituted thienyl. In some embodiments, Cy is a substituted pyrazolyl. In some embodiments, Cy is an unsubstituted pyrazolyl. In some embodiments, Cy is a substituted imidazolyl. In some embodiments, Cy is an unsubstituted imidazolyl. In some embodiments, Cy is a substituted oxazolyl. In some embodiments, Cy is an unsubstituted oxazolyl. In some embodiments, Cy is a substituted isoxazolyl. In some embodiments, Cy is an unsubstituted isoxazolyl. In some embodiments, Cy is a substituted thiazolyl. In some embodiments, Cy is an unsubstituted thiazolyl. In some embodiments, Cy is a substituted isothiazolyl. In some embodiments, Cy is an unsubstituted isothiazolyl. In some embodiments, Cy is a substituted triazolyl. In some embodiments, Cy is an unsubstituted triazolyl. In some embodiments, Cy is a substituted oxadiazolyl. In some embodiments, Cy is an unsubstituted oxadiazolyl. In some embodiments, Cy is a substituted thiadiazolyl. In some embodiments, Cy is an unsubstituted thiadiazolyl. In some embodiments, Cy is a 6-membered monocyclic heteroaryl ring. In some embodiments, Cy is a 6-membered monocyclic heteroaryl ring having one heteroatom selected from the group consisting of S, N and O. In some embodiments, Cy is a 6-membered monocyclic heteroaryl ring having two heteroatoms selected from the group consisting of S, N and O. In some embodiments, Cy is a 6-membered monocyclic heteroaryl ring having 3 heteroatoms selected from the group consisting of S, N and O. In some embodiments, Cy is a substituted pyridyl. In some embodiments, Cy is an unsubstituted pyridyl. In some embodiments, Cy is a substituted pyridadinyl. In some embodiments, Cy is an unsubstituted pyridadinyl. In some embodiments, Cy is a substituted pyrimidinyl. In some embodiments, Cy is an unsubstituted pyrimidinyl. In some embodiments, Cy is a substituted pyrazinyl. In some embodiments, Cy is an unsubstituted pyrazinyl. In some embodiments, Cy is a substituted triazinyl. In some embodiments, Cy is an unsubstituted triazinyl. In some embodiments, Cy is fused to one or more arbitrarily substituted carbocyclic groups, optionally substituted heterocyclic groups, optionally substituted aryl groups, or optionally substituted heteroaryl groups. , Arbitrarily substituted heteroaryl rings, wherein the bonding point is a heteroaryl ring, or a carbocyclic group, a heterocyclic group, an aryl group or a heteroaryl group, as long as the valence allows. Above one or two or more. In some embodiments, Cy is a bicyclic heteroaryl ring. In some embodiments, Cy is an arbitrarily substituted heteroaryl ring fused to an arbitrarily substituted phenyl ring. In some embodiments, Cy is a replacement indrill. In some embodiments, Cy is an unsubstituted indrill. In some embodiments, Cy is a substituted isoindolyl. In some embodiments, Cy is an unsubstituted isoindolyl. In some embodiments, Cy is a substituted indazolyl. In some embodiments, Cy is an unsubstituted indazolyl. In some embodiments, Cy is a substituted benzothienyl. In some embodiments, Cy is an unsubstituted benzothienyl. In some embodiments, Cy is a substituted isobenzothienyl. In some embodiments, Cy is an unsubstituted isobenzothienyl. In some embodiments, Cy is a substituted benzofuranyl. In some embodiments, Cy is an unsubstituted benzofuranyl. In some embodiments, Cy is a substituted benzoisofuranyl. In some embodiments, Cy is an unsubstituted benzoisofuranyl. In some embodiments, Cy is a substituted benzoimidazolyl. In some embodiments, Cy is an unsubstituted benzoimidazolyl. In some embodiments, Cy is a substituted benzoxazolyl. In some embodiments, Cy is an unsubstituted benzoxazolyl. In some embodiments, Cy is a substituted benzoisoxazolyl. In some embodiments, Cy is an unsubstituted benzoisoxazolyl. In some embodiments, Cy is a substituted benzothiazolyl. In some embodiments, Cy is an unsubstituted benzothiazolyl. In some embodiments, Cy is a substituted benzoisothiazolyl. In some embodiments, Cy is an unsubstituted benzoisothiazolyl. In some embodiments, Cy is a substituted benzotriazolyl. In some embodiments, Cy is an unsubstituted benzotriazolyl. In some embodiments, Cy is a substituted benzoxaziazolyl. In some embodiments, Cy is an unsubstituted benzoxaziazolyl. In some embodiments, Cy is a substituted quinolinyl. In some embodiments, Cy is an unsubstituted quinolinyl. In some embodiments, Cy is a substituted isoquinolinyl. In some embodiments, Cy is an unsubstituted isoquinolinyl. In some embodiments, Cy is a substituted synnolinyl. In some embodiments, Cy is an unsubstituted synnolinyl. In some embodiments, Cy is a substituted quinoxalinyl. In some embodiments, Cy is an unsubstituted quinoxalinyl. In some embodiments, Cy is a substituted phthalazinyl. In some embodiments, Cy is an unsubstituted phthalazinyl. In some embodiments, Cy is a substituted quinazolinyl. In some embodiments, Cy is an unsubstituted quinazolinyl. In some embodiments, Cy

Here, X'may be freely connected to a position where the valences match. In some embodiments, Cy

Here, X'may be freely connected to a position where the valences match. In some embodiments, Cy

Here, X'may be freely connected to a position where the valences match. In some embodiments, Cy

Here, X'may be freely connected to a position where the valences match. In some embodiments, Cy

Here, X'may be freely connected to a position where the valences match. In some embodiments, Cy

Here, X'may be freely connected to a position where the valences match. In some embodiments, Cy

Here, X'may be freely connected to a position where the valences match. In some embodiments, Cy

Here, X'may be freely connected to a position where the valences match. In some embodiments, Cy

Here, X'may be freely connected to a position where the valences match. In some embodiments, Cy

Here, X'may be freely connected to a position where the valences match. In some embodiments, Cy

Here, X'may be freely connected to a position where the valences match. In some embodiments, Cy

Here, X'may be freely connected to a position where the valences match. In some embodiments, Cy

Here, X'may be freely connected to a position where the valences match. In some embodiments, Cy

Here, X'may be freely connected to a position where the valences match. In some embodiments, Cy

Here, X'may be freely connected to a position where the valences match. In some embodiments, Cy

Here, X'may be freely connected to a position where the valences match. In some embodiments, Cy

Here, X'may be freely connected to a position where the valences match. In some embodiments, Cy

Here, X'may be freely connected to a position where the valences match. In some embodiments, Cy

Here, X'may be freely connected to a position where the valences match. In some embodiments, Cy

Here, X'may be freely connected to a position where the valences match. In some embodiments, Cy

Here, X'may be freely connected to a position where the valences match. In some embodiments, Cy

Here, X'may be freely connected to a position where the valences match. In some embodiments, Cy

Here, X'may be freely connected to a position where the valences match. In some embodiments, Cy

Here, X'may be freely connected to a position where the valences match. In some embodiments, Cy

Here, X'may be freely connected to a position where the valences match. In some embodiments, Cy

Here, X'may be freely connected to a position where the valences match. In some embodiments, Cy

Here, X'may be freely connected to a position where the valences match. In some embodiments, Cy

Here, X'may be freely connected to a position where the valences match. In some embodiments, Cy

Here, X'may be freely connected to a position where the valences match. In some embodiments, Cy

Here, X'may be freely connected to a position where the valences match. In some embodiments, Cy

Here, X'may be freely connected to a position where the valences match. In some embodiments, Cy

Here, X'may be freely connected to a position where the valences match. In some embodiments, Cy

Here, X'may be freely connected to a position where the valences match. In some embodiments, Cy

Here, X'may be freely connected to a position where the valences match. In some embodiments, Cy

Here, X'may be freely connected to a position where the valences match.

である。ある態様において、少なくとも１個のＲ^Ｘ’は、

である。ある態様において、少なくとも１個のＲ^Ｘ’は、

である。ある態様において、少なくとも１個のＲ^Ｘ’は、

である。ある態様において、少なくとも１個のＲ^Ｘ’は、

である。ある態様において、少なくとも１個のＲ^Ｘ’は、

である。ある態様において、少なくとも１個のＲ^Ｘ’は、

である。ある態様において、少なくとも１個のＲ^Ｘ’は、

である。ある態様において、少なくとも１個のＲ^Ｘ’は、

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である。ある態様において、少なくとも１個のＲ^Ｘ’は、

である。ある態様において、少なくとも１個のＲ^Ｘ’は、

である。ある態様において、少なくとも１個のＲ^Ｘ’は、

である。ある態様において、少なくとも１個のＲ^Ｘ’は、

である。ある態様において、少なくとも１個のＲ^Ｘ’は、

である。ある態様において、少なくとも１個のＲ^Ｘ’は、

である。ある態様において、少なくとも１個のＲ^Ｘ’は、

である。ある態様において、少なくとも１個のＲ^Ｘ’は、

である。ある態様において、少なくとも１個のＲ^Ｘ’は、

である。ある態様において、少なくとも１個のＲ^Ｘ’は、

である。ある態様において、少なくとも１個のＲ^Ｘ’は、

である。ある態様において、少なくとも１個のＲ^Ｘ’は、

である。ある態様において、少なくとも１個のＲ^Ｘ’は、

である。ある態様において、少なくとも１個のＲ^Ｘ’は、

である。ある態様において、少なくとも１個のＲ^Ｘ’は、

である。ある態様において、少なくとも１個のＲ^Ｘ’は、

である。ある態様において、少なくとも１個のＲ^Ｘ’は、

である。ある態様において、少なくとも１個のＲ^Ｘ’は、

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である。ある態様において、少なくとも１個のＲ^Ｘ’は、

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である。ある態様において、少なくとも１個のＲ^Ｘ’は、

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である。ある態様において、少なくとも１個のＲ^Ｘ’は、

である。ある態様において、少なくとも１個のＲ^Ｘ’は、

である。ある態様において、少なくとも１個のＲ^Ｘ’は、

である。ある態様において、少なくとも１個のＲ^Ｘ’は、

である。ある態様において、少なくとも１個のＲ^Ｘ’は、

である。ある態様において、少なくとも１個のＲ^Ｘ’は、

である。ある態様において、少なくとも１個のＲ^Ｘ’は、

である。 In the compounds of formula (II) or (V), Cy may be substituted with one or two or more of R X 'group. In certain embodiments, at least one of R X 'is H. In certain embodiments, at least two R X 'groups are H. In some embodiments, at least three of R X 'groups are H. In certain embodiments, at least four R X 'groups are H. In certain embodiments, at least one of R X 'is halogen. In certain embodiments, at least one of R X 'is F. In certain embodiments, at least one of R X 'is is Cl. In certain embodiments, at least one of R X 'is Br. In certain embodiments, at least one of R X 'is I (iodine). In certain embodiments, at least one of R X 'is a substituted acyl. In certain embodiments, at least one of R X 'are, -C (= O) N ( R A1') 2. In certain embodiments, at least one of R X 'are, -C (= O) NHR A1 ' is. In certain embodiments, at least one of R X 'is -C (= O) NH (C 1-6 alkyl). In certain embodiments, at least one of R X 'is -C (= O) NHMe. In certain embodiments, at least one of R X 'is -C (= O) NH 2. In certain embodiments, at least one of R X 'is unsubstituted acyl. In certain embodiments, at least one of R X 'is acetyl. In certain embodiments, at least one of R X 'is a substituted alkyl. In certain embodiments, at least one of R X 'is a substituted methyl. In certain embodiments, at least one of R X 'is unsubstituted alkyl. In certain embodiments, at least one of R X 'is a C 1-6 alkyl. In certain embodiments, at least one of R X 'is methyl. In certain embodiments, at least one of R X 'is ethyl. In certain embodiments, at least one of R X 'is propyl. In certain embodiments, at least one of R X 'is butyl. In certain embodiments, at least one of R X 'is a substituted alkenyl. In certain embodiments, at least one of R X 'is unsubstituted alkenyl. In certain embodiments, at least one of R X 'is a substituted alkynyl. In certain embodiments, at least one of R X 'is unsubstituted alkynyl. In certain embodiments, at least one of R X 'is a substituted carbocyclyl. In certain embodiments, at least one of R X 'is unsubstituted carbocyclyl. In certain embodiments, at least one of R X 'is a substituted heterocyclyl. In certain embodiments, at least one of R X 'is unsubstituted heterocyclyl. In certain embodiments, at least one of R X 'is a substituted aryl. In certain embodiments, at least one of R X 'is unsubstituted aryl. In certain embodiments, at least one of R X 'is a substituted phenyl. In certain embodiments, at least one of R X 'is unsubstituted phenyl. In some embodiments, 'at least one of R X, is substituted heteroaryl. In certain embodiments, at least one of R X 'is unsubstituted heteroaryl. In certain embodiments, at least one of R X 'is a substituted pyridyl. In certain embodiments, at least one of R X 'is unsubstituted pyridyl. In certain embodiments, at least one of R X 'are, -OR A1' is. In certain embodiments, at least one of R X 'is -O (C 1-6 alkyl). In some embodiments, 'at least one of R X, is -OMe. In certain embodiments, at least one of R X 'is -OH. In certain embodiments, at least one of R X 'are, -N (R A1') 2. In certain embodiments, at least one of R X 'is -NH 2. In certain embodiments, at least one of R X 'are, -SR A1' is. In certain embodiments, at least one of R X 'is -SH. In certain embodiments, at least one of R X 'are, -NR A1' C (= O ) N (R A1 ') 2. In certain embodiments, at least one of R X 'are, -NHC (= O) N ( R A1') 2. In certain embodiments, at least one of R X 'are, -NHC (= O) NHR A1 ' is. In certain embodiments, at least one of R X 'is -NHC (= O) NH (C 1-6 alkyl). In certain embodiments, at least one of R X 'is -NHC (= O) NHMe. In certain embodiments, at least one of R X 'is -NHC (= O) NH 2. In certain embodiments, at least one of R X 'are, -NR A1' is a C (= O) NHR A1 ' . In certain embodiments, at least one of R X 'are, -NR A1' is a C (= O) NH 2. In certain embodiments, at least one of R X 'are, -NR A1' is S (= O) 2 R A1 '. In certain embodiments, at least one of R X 'are, -NHS (= O) 2 R A1' is. In certain embodiments, at least one of R X 'is -NHS (= O) 2 (C 1-6 alkyl). In certain embodiments, at least one of R X 'is -NHS (= O) 2 Me. In certain embodiments, at least one of R X 'are, -S (= O) 2 N (R A1') 2. In certain embodiments, at least one of R X 'are, -S (= O) 2 N (R A1') 2. In certain embodiments, at least one of R X 'are, -S (= O) 2 N (C 1-6 alkyl) 2. In certain embodiments, at least one of R X 'is -S (= O) 2 NH ( C 1-6 alkyl). In certain embodiments, at least one of R X 'is -S (= O) 2 NH ( t-Bu). In certain embodiments, at least one of R X 'is -S (= O) 2 NH 2 . In some embodiments, 'at least one of R X,

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is. In some embodiments, 'at least one of ^{R X,}

Is.

In some embodiments, the compounds of the invention are compounds of formula (A) or pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers thereof. It is an isotope-labeled derivative or prodrug. In some embodiments, the compounds of the invention are compounds of formula (A), or pharmaceutically acceptable salts thereof. In some embodiments, the compounds of the invention are compounds of formula (I-11) or pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers thereof. A body, isotope-labeled derivative or prodrug. In some embodiments, the compounds of the invention are compounds of formula (I-11), or pharmaceutically acceptable salts thereof. In some embodiments, the compounds of the invention are compounds of formula (II) or pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers thereof. It is an isotope-labeled derivative or prodrug. In some embodiments, the compounds of the invention are compounds of formula (II), or pharmaceutically acceptable salts thereof. In some embodiments, the compounds of the invention are compounds of formula (V) or pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers thereof. It is an isotope-labeled derivative or prodrug. In some embodiments, the compounds of the invention are compounds of formula (V), or pharmaceutically acceptable salts thereof.

In some embodiments, the compounds of the invention are:
・ Shows kinase inhibitory activity
Transforming growth factor b Shows the ability to inhibit activated kinase-1 (TAK1), hematopoietic cell kinase (HCK), or both TAK1 and HCK,
• Shows the ability to inhibit hematopoietic progenitor cell kinase 1 (HPK1, also known as mitogen-activated protein kinase kinase kinase kinase 1 or MAP4K1).
Shows the ability to inhibit both Bruton's tyrosine kinase (BTK), v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homologue (SRC) family of kinases, or both BTK and SRC.
• Shows cytotoxic or growth-inhibitory effects on WM cell lines maintained in vitro or in animal studies using scientifically acceptable cancer cell xenograft models; and / or existing chemotherapies Includes those that exhibit a better therapeutic profile than therapeutic agents (eg, optimal safety and healing effect).

As used herein, "kinase" catalyzes the transfer of γ-phosphate from ATP to a hydroxyl group on the side chain of Ser / Thr or Tyr in proteins and peptides, and ultimately varies. Refers to a large class of enzymes involved in the regulation of important cellular functions (perhaps especially: signaling, differentiation and proliferation). It is estimated that there are about 2,000 characteristic protein kinases in the human body, all of which are the same second substrate, even though each of them phosphorylates a particular protein / peptide substrate. It binds to ATP, which is a highly preserved pocket. About 50% of the known oncogene products are protein tyrosine kinase PTKs, and their kinase activity has been shown to result in cell transformation.

In some embodiments, the kinase to be inhibited is involved in the myeloid differentiation primary response gene (88) (MYD88) signaling pathway. For example, the kinase is transforming growth factor b activated kinase-1 (TAK1) or hematopoietic cell kinase (HCK). In some embodiments, the compounds of the invention inhibit TAK1, HCK, or both TAK1 and HCK.

The myeloid differentiation primary response gene (88) (MYD88) L265P is a somatic mutation that is widely expressed in WM patients and supports NF-NFκB signaling through stimulation of BTK, IRAK1 / 4, and TAK1. MYD88 is an adapter molecule for Toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) signaling except TLR-3. Following stimulation of TLR or IL-1R, MYD88 was recruited as a homodimer to the activated receptor complex, which was then complexed with interleukin-1 receptor-related kinase 4 (IRAK4). , Activates IRAK1 and IRAK2. Neoplasmic necrosis factor receptor-related factor 6 (TRAF6) is then activated by IRAK1 leading to activation of NFκB via phosphorylation of IκBα and activation of TAK1.

Transforming growth factor b activated kinase-1 (TAK1; also known as MAP3K7) is a member of the serine / threonine protein kinase family. This kinase mediates signal transduction induced by TGF beta and morphogenetic proteins (BMPs) and regulates a variety of cellular functions, including transcriptional regulation and apoptosis. TAK1 knockout is embryo-lethal for mice. Conditional knockdown of TAK1 in adult mice results in systemic inflammation, splenomegaly, degeneration in the heart, kidney and liver, and increased proliferation and differentiation of bone marrow progenitor cells. TAK1 is located downstream of Myd88, Bruton's tyrosine kinase (BTK) and interleukin-1 receptor-related kinase (IRAK) and has been studied for its role in innate immunity, inflammatory response and Ras-dependent cancers. ..

Hematopoietic cell kinase (HCK) is a non-receptor tyrosine-protein kinase found in hematopoietic cells and is known to interact with Bruton's tyrosine kinase (BTK) upon activation by B cell receptors (Proc). Natl Acad Sci USA. 1994 91 (17), 8152-55). HCK transmits signals from cell surface receptors and regulates the innate immune response, including neutrophil, monocyte, macrophage and mast cell function, phagocytosis, cell survival and proliferation, cell adhesion and migration. , Play an important role. It acts not only on receptors that bind to the Fc region of immunoglobulins, such as FCGR1A and FCGR2A, but also downstream of receptors for integrins such as CSF3R, PLAUR, IFNG, IL2, IL6 and IL8 and ITGB1 and ITGB2. To do. During the process of phagocytosis, it mediates the mobilization of secretory lysosomes, degranulation, and activation of NADPH oxidase, causing respiratory bursts. It also plays a role in the release of inflammatory molecules, promoting actin cytoskeleton rearrangement and actin polymerization, as well as the formation of podsomes and cell processes.

Hematopoietic progenitor kinase kinase 1 (HPK1) is a member of the Ste20 serine / threonine kinase superfamily limited to hematopoietic cells. HPK1 is also called mitogen-activated protein kinase kinase kinase kinase 1 (MAP4K1). HPK1 is a tissue-specific upstream activator of the MEKK / JNK / SAPK signaling pathway. HPK1 reduces T cell receptor (TCR) signaling activity and T cell proliferation by phosphorylating the adapter protein SLP-76. HPK1 in the cytosol is recruited to the TCR complex, and its kinase activity is induced by TCR engagement. Overexpression of HPK1 suppresses TCR-induced activation of AP-1-dependent gene transcription in a kinase-dependent manner, because the kinase activity of HPK1 inhibits the Erk MAPK pathway. It suggests that it is needed. Blockage of this Erk MAPK pathway is thought to be an inhibitory mechanism that negatively regulates TCR-induced IL-2 gene transcription (Immunol. Res. 2012, 54 (1-3), 262-65). In some embodiments, the compounds of the invention, eg, compounds of formulas (A), (I-11), (II) or (V) (eg, compounds of formulas (A-1)-(A-18)) are HPK1. Inhibits.

In some embodiments, the compounds of the invention are selective inhibitors of TAK1, HCK or HPK1. The term "selective inhibitor", as used herein, refers to TAK1, HCK or HPK1, although the compound does not act on a variety of kinases as compared to many kinase inhibitors of the prior art. It is understood to mean that it acts specifically on the contrary. In some embodiments, the compounds of the invention inhibit one or more kinases, such as BTK or SRC family kinases, in addition to TAK1, HCK or HPK1. In certain embodiments of the present invention, the specificity of the inhibitor is indicated by an IC ₅₀ value. In some embodiments, the _{IC 50} values for some selective inhibitors, TAK1, for HCK or HPK1 <is a 100 [mu] M, for other kinases> is 100 [mu] M.

IC ₅₀ values are defined as the concentration of inhibitor required to inhibit 50% of kinase activity. In certain embodiments, the compounds of the present invention, _{IC 50} values may indicate <100 [mu] M. In certain other embodiments, the compound, _{IC 50} value showing the <50 [mu] M. In certain other embodiments, the compound shows an _{IC 50} value <40 [mu] M. In certain other embodiments, the compound, _{IC 50} value showing the <30 [mu] M. In certain other embodiments, the compound, _{IC 50} value showing the <20 [mu] M. In certain other embodiments, the compound, _{IC 50} value showing the <10 [mu] M. In certain other embodiments, the compound shows an _{IC 50} value <7.5 [mu] M. In some embodiments, the compound, _{IC 50} value showing the <5 [mu] M. In certain other embodiments, the compound shows an _{IC 50} value <2.5 [mu] M. In some embodiments, the compound, _{IC 50} value showing the <1 [mu] M. In some embodiments, the compounds exhibit _{IC 50} values <0.75μM. In some embodiments, the compound, _{IC 50} value showing the <0.5 [mu] M. In some embodiments, the compounds exhibit _{IC 50} values <0.25 [mu] M. In some embodiments, the compounds exhibit _{IC 50} values <0.1 [mu] M. In certain other embodiments, the compound shows an _{IC 50} value <75 nM. In certain other embodiments, the compound, _{IC 50} value showing the <50 nM. In certain other embodiments, the compound shows an _{IC 50} value <25 nM. In certain other embodiments, the compound shows an _{IC 50} value <10 nM. In other embodiments, the compounds exhibit _{IC 50} values <7.5 nM. In other embodiments, the compound, _{IC 50} value showing the <5 nM.

である。 In some embodiments, the compounds of the invention (eg, any one of formulas (A), (I-11), (II) or (V)) selectively inhibit HCK. In some embodiments, the compounds of the invention (eg, compounds of formulas (A), (I-11), (II) or (V)) selectively inhibit TAK1. Non-limiting examples of selective TAK1 inhibitors are:

Is.

である。 In some embodiments, the compounds of the invention (eg, compounds of formulas (A), (I-11), (II) or (V)) inhibit both TAK1 and HCK. Non-limiting examples of TAK1 / HCK double inhibitors are:

Is.

である。 In some embodiments, the compounds of the invention (eg, compounds of formulas (A), (I-11), (II) or (V)) selectively inhibit HPK1. Non-limiting examples of selective HPK1 inhibitors are:

Is.

Also provided are Bruton's tyrosine kinase (BTK), interleukin-1 receptor-related kinase 1 (IRAK1), interleukin-1 receptor-related kinase 4 (IRAK4), and X chromosome. Treat B cell neoplasms in combination with supraventricular kinase (BMX), phosphoinositide 3-kinase (PI3K), transforming growth factor b-activated kinase-1 (TAK1), and / or Src family kinase inhibitors How to do it. In some embodiments, one or more compounds of the invention are used in combination with an inhibitor of phosphoinositide 3-kinase delta isoform (PI3Kδ). In some embodiments, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more combinations of the agents described herein are used to treat WM. In some embodiments, the agents described herein are Bruton's tyrosine kinase (BTK), interleukin-1 receptor-related kinase 1 (IRAK1), interleukin-1 receptor-related kinase 4 (IRAK4), X chromosome. It is used in combination with an inhibitor of upper bone marrow kinase (BMX), phosphoinositide 3-kinase (PI3K), transforming growth factor b-activated kinase-1 (TAK1), and / or Src family kinase.

Bruton's tyrosine kinase (BTK) is an important signaling enzyme expressed in all hematopoietic cell types except T lymphocytes and natural killer cells. BTK plays an essential role in linking cell surface B cell receptor BCR stimulation to the downstream intracellular response in the B cell signaling pathway. BTK is an important regulator of B cell developmental activation signaling and survival (Kurosaki, Curr. Op. Imm., 2000, 276-281; Schaeffer and Schwartzberg, Curr. Op. Imm., 2000, 282. -288). In addition, BTK is mediated by many other hematopoietic cell signaling pathways, such as Toll-like receptors (TLRs) and cytokine receptors in macrophages, TNF-α production, IgE receptor (FcepsilonRI) signaling in mast cells, B cell lineage Plays a role in inhibiting Fas / APO-1 apoptotic signaling in lymphoid cells and in collagen-stimulated platelet aggregation. For example, CA Jeffries, et al., J. Biol. Chem., 2003, 278, 26258-26264; NJ Horwood, et al., J. Exp. Med., 2003, 197, 1603-1611; Iwaki et al., J. Biol. Chem., 2005, 280 (48), 40261-40270; Vassilev et al., J. Biol. Chem., 1999, 274 (3), 1646-1656; and Quek et al., Curr. Biol ., 1998, 8 (20), 1137-1140. Activated Btk interacts with MyD88 and TRIF and promotes activation of MyD88-dependent and TRIF-dependent pathways (Nature Immunology, 2011, 12, 416-424).

BTK inhibitors are well known in the art and include, for example, ibrutinib and benzonaphthyridinone (see US Patent Provisional Application U.S.S.N. 61 / 716,273 filed October 19, 2012). Further non-limiting examples of BTK inhibitors are disclosed in WO 1999/054286, WO 2013/010380, WO 2009/137596, WO 2011/029043, WO 2010/056875, WO 2000/056737 and WO 2013/067277. ..

IRAK1 and 4 are serine / threonine-protein kinases that play an important role in initiating the innate immune response against foreign pathogens. They are involved in Toll-like receptors (TLRs) and IL-1R signaling pathways and are rapidly recruited by MYD88 to receptor-signaling complexes upon TLR activation. Association with MYD88 results in IRAK4 phosphorylation of IRAK1 followed by IRAK1 autophosphorylation and kinase activation (Immunity, 1997, 7 (6), 837-47). IRAK4-/-mice have disrupted cellular responses to various IL-1 and TLR ligands, severely impairing their response to viral and bacterial loads. IRAK1 − / − mice show a similar but partial response.

IRAK1 and IRAK4 inhibitors are well known in the art, such as WO 2003/030902, WO 2012/007375, GM Buckely et al., Biorg. Med. Chem. Lett., 2008, 18, 3211-3214 and GM. As described in Buckely et al., Biorg. Med. Chem. Lett., 2008, 18, 3656-3660, WO2013 / 074986, and US patent provisional application USSN 61 / 727,640 filed November 16, 2012. including.

のもの、またはそのアナログである。
「Ｘ染色体上骨髄」キナーゼ（BMX、別名ETK）は、非受容体型チロシンキナーゼであり、ホスファチジルイノシトール−３キナーゼ（PI-3K）およびv-src肉腫（Schmidt-Ruppin A-2）ウイルス癌遺伝子相同体（SRC）の下流で活性化されるが、その基質は知られていない。ポジショナルスキャニングペプチドライブラリースクリーニングにより、ホスホチロシン（ｐＹ）を−１位においてプライミングすることについての顕著な優先性が明らかとなった。潜在的な基質は、完全活性のためにキナーゼドメインｐＹｐＹ部位を有することが必要とされる複数のチロシンキナーゼを含む。BMXは、SRCによるＹ５７６のリン酸化に続いて接着斑キナーゼ（FAK）の残基Ｙ５７７をリン酸化することが明らかとなっている。さらに、RNA干渉によるBMXの欠失、およびBmx陰性（Bmx⁻）マウスからのマウス胚線維芽細胞（MEF）は、FAKシグナル伝達の障害を示した。インスリン受容体（IR）のリン酸化は、同様に、BMXの欠失により低下し、Bmx⁻マウスにおける肝臓のIRリン酸化も同様であった。しかし、グルコース耐性は増大し、このことは、AKTホスファターゼPHLPPの活性の著しく代償的な低下を反映している。これらの知見により、BMXが、複数のキナーゼ経路の中心的調節因子として機能する機構が明らかとなる。
BMX阻害剤は、当該分野において周知であり、例えば、U.S.S.N. 61/716,273および61/717,345において記載されるものを含み、これらの両方の内容は、本明細書に参考により組み込まれる。ある態様において、BMX阻害剤は、式：

のもの、またはそのアナログである。 In some embodiments, the IRAK4 inhibitor is

Or an analog of it.
"X-chromosomal bone marrow" kinase (BMX, also known as ETK) is a non-receptor tyrosine kinase that is homologous to phosphatidylinositol-3 kinase (PI-3K) and v-src sarcoma (Schmidt-Ruppin A-2) viral oncogenes. It is activated downstream of the body (SRC), but its substrate is unknown. Positional scanning peptide library screening revealed a significant priority for priming phosphotyrosine (pY) at position -1. Potential substrates include multiple tyrosine kinases that are required to have a kinase domain pYpY site for full activity. BMX has been shown to phosphorylate residue Y577 of focal adhesion kinase (FAK) following phosphorylation of Y576 by SRC. In addition, RNA interference-induced BMX deletion and mouse embryonic fibroblasts (MEF) from ^{Bmx-negative (Bmx −) mice showed impaired FAK signaling.} Insulin receptor (IR) phosphorylation was similarly reduced by BMX deletion, as was liver IR phosphorylation in ^Bmx-mice. However, glucose tolerance increased, which reflects a markedly compensatory decrease in the activity of the AKT phosphatase PHLPP. These findings reveal a mechanism by which BMX functions as a central regulator of multiple kinase pathways.
BMX inhibitors are well known in the art and include, for example, those described in USSN 61 / 716,273 and 61 / 717,345, both of which are incorporated herein by reference. In some embodiments, the BMX inhibitor is of the formula:

Or an analog of it.

Phosphatidylinositol 3-kinase (PI3-kinase or PI3K) is a family of enzymes involved in cell functions such as cell growth, proliferation, differentiation, motility, survival and intracellular transport, and these functions are then followed by. Involved in cancer. PI3K is a family of related intracellular signaling enzymes capable of phosphorylating the hydroxyl group at position 3 of the inositol ring of phosphatidylinositol (Ptdlns). Phosphatidylinositol 3-kinase consists of a regulatory subunit of 85 kDa and a catalytic subunit of 110 kDa. The protein encoded by the PI3KCA gene represents the catalytic subunit, which uses ATP to phosphorylate phosphatidylinositol (Ptdlns), Ptdlns4P and Ptdlns (4,5) P2. Of particular importance is the PI3K delta isoform, which is expressed on leukocytes and is primarily involved in B cell signaling, development and survival.

PI3K inhibitors are well known in the art and include, for example, those described in International PCT Publications WO 2013/088404, WO 2012/068096 and WO 2013/052699, which are incorporated herein by reference.

またはそのアナログである。 In some embodiments, the PI3K inhibitor is

Or its analog.

The compounds of the invention may be combined with other kinase inhibitors to treat WM or other B cell neoplasms. In some embodiments, the compounds of the invention are administered with an inhibitor of Bruton's tyrosine kinase (BTK) to treat WM or other B cell neoplasms. In some embodiments, the compounds of the invention are administered with an inhibitor of interleukin-1 receptor-related kinase 1 (IRAK1) to treat WM or other B cell neoplasms. In some embodiments, the compounds of the invention are administered with an inhibitor of phosphoinositide 3-kinase (PI3K) to treat WM or other B cell neoplasms. In some embodiments, the compounds of the invention are administered with an inhibitor of phosphoinositide 3-kinase delta isoform (PI3Kδ) to treat WM or other B cell neoplasms. In some embodiments, the compounds of the invention are administered with two of any inhibitors of BTK, IRAK1 or PI3K to treat WM or other B cell neoplasms. In some embodiments, the compounds of the invention are administered with more than two of any inhibitors of BTK, IRAK1 or PI3K to treat WM or other B cell neoplasms.

BTK inhibitors, IRAK1 inhibitors, IRAK4 inhibitors and / or PI3K inhibitors can be administered to a subject simultaneously or sequentially.

The "subject" or "patient" intended for administration includes any animal. In some embodiments, the subject is, but is not limited to, humans, commerce-related mammals (eg, cows, pigs, horses, ducks, goose, cats and / or dogs), birds (eg, commerce-related birds, eg, eg. Included are chickens, ducks, geese and / or worms), as well as laboratory animals (eg, mice, rats, non-human primates). A subject in need of treatment is a subject identified as having a B cell neoplasm, i.e., the subject has been diagnosed by a physician as having a B cell neoplasm (eg, using methods well known in the art). hand). In some embodiments, a subject in need of treatment is a subject who has or is suspected of developing a B cell neoplasm, eg, a subject who exhibits one or more symptoms that are indicators of B cell neoplasms. .. The term "subject in need of treatment" further includes people who once had a B cell neoplasm but whose signs and / or symptoms are in remission (ie, the cancer is in remission). One or more symptoms or clinical features of B cell neoplasms include, but are not limited, asymptomatic, localized or generalized peripheral lymphadenoma, plasmacytic difference, bone marrow lesions ( Involvement), autoimmune thrombocytopenia, peripheral blood villous lymphocytes, terminal organ damage (hypercalcemia, renal failure bone lesions), recurrent infection, elevated creatinine, hyperuricemia and hypoalbuminemia. ..

In some embodiments, the subject is diagnosed with Waldenström macroglobulinemia (WM). Subjects may exhibit one or more signs, symptoms or clinical features of WM, including anemia, hyperviscosity, neuropathy, coagulopathy, splenomegaly, hepatomegaly, adenoma and IgM serum paraprotein. In some embodiments, the subject is diagnosed with WM based on the subject having a mutation at position 38182641 on chromosome 3p22.2. In some embodiments, the mutation results in a single nucleotide change from T to C in the MYD88 gene. In some embodiments, the mutation results in a leucine to proline amino acid change at position 265 in the MYD88 gene. Mutations are in biological samples obtained from a subject using any suitable method known in the art, including, but not limited to, direct sequencing of nucleic acid molecules, HPLC analysis, DNA chip technology and mass spectrometry. Can be detected with. Non-limiting examples of biological samples include bone marrow, lymph nodes, spleen and blood.

The terms "administer," "administer," or "administer," as used herein, to transplant, absorb, digest, or inject a compound of the invention or a pharmaceutical composition thereof. Refers to doing or inhaling.

As used herein, the terms "treatment," "treating," and "treating" are used to reverse, alleviate, delay the onset, or inhibit its progression of B cell neoplasms. Refers to doing. In some embodiments, the treatment may be administered after one or more signs or symptoms have developed or have been observed. In other embodiments, the treatment may be administered in the absence of B cell neoplastic signs or symptoms. For example, treatment may be administered to susceptible individuals prior to the onset of symptoms (eg, considering the history of symptoms and / or genetic or other susceptibility factors). Treatment may also be continued after the symptoms have resolved, eg, to delay or prevent recurrence.

An "effective amount" of a compound of the invention refers to an amount sufficient to elicit the desired biological response, i.e., to treat a B cell neoplasm. As will be appreciated by those skilled in the art, the effective amounts of the compounds of the invention are the desired biological endpoint, the pharmacokinetics of the compound, the condition being treated, the mode of administration, and the age of the subject. And can change depending on factors such as health. Effective amounts are required, but not limited, to delay, alleviate, inhibit, ameliorate, or reverse one or more signs and / or symptoms associated with B cell neoplasms. Includes quantity. In the treatment of Waldenström macroglobulinemia, it reduces IgM serum paraprotein levels, reduces anemia, reduces hyperviscosity, reduces neuropathy, reduces coagulopathy, reduces splenomegaly, hepatomegaly. It can refer to a large reduction and a reduction of adenoma.

The effective amount of the compound can vary from about 0.001 mg / kg to about 1000 mg / kg in one or more doses over a day or days (depending on the mode of administration). In some embodiments, the effective amounts are from about 0.001 mg / kg to about 1000 mg / kg, from about 0.01 mg / kg to about 750 mg / kg, from about 0.1 mg / kg to about 500 mg / kg, about 1.0 mg / kg. It can vary from about 250 mg / kg, about 1.0 mg / kg to about 100 mg / kg, and from about 10.0 mg / kg to about 150 mg / kg.

One or more additional pharmaceutical agents, such as anti-cancer agents (eg, chemotherapeutic agents), anti-inflammatory agents, steroids, immunosuppressants, radiation therapy or other agents, are used in the treatment of B cell neoplasms according to the invention. It can be used in combination with a compound. One or more additional pharmaceutical agents can be administered to the subject simultaneously or continuously.

As exemplary chemotherapeutic agents, alkylating agents such as nitrogen mustard, ethyleneimine, methylmelamine, alkylsulfonate, nitrosourea and triazene; antimetabolites such as folic acid analogs, pyrimidine analogs, especially fluorouracil and citocin arabinoside, And purine analogs; natural products such as binca alkaloids, epipodophylrotoxins, antibiotics, enzymes and biological response modifiers; and various products such as platinum coordination complexes, anthracendions, substituted ureas such as hydroxy. Examples include urea, methylhydrazine derivatives, and adrenocorticoid inhibitors.

Exemplary chemotherapeutic agents are also anthracycline antibiotics, actinomycin D, plicamycin, puromycin, gramicidin D, paclitaxel, corhitin, cytocaracin B, emetin, mitanthin, amsacline, cisplatin, carboplatin, mitomycin, altretamine, cyclo Includes phosphamide, lomustine and carmustine.

In yet another aspect, the invention is an effective amount of a compound of the invention and a pharmaceutically acceptable salt, solvate, hydrate, polymorph, for use in the treatment of B cell neoplasms. Provided are pharmaceutical compositions comprising co-crystals, tautomers, stereoisomers, isotope-labeled derivatives, and prodrugs, and optionally pharmaceutically acceptable excipients. In some embodiments, the invention provides the compounds of the invention, as well as pharmaceutically acceptable salts and compositions thereof, for use in the treatment of B cell neoplasms. In some embodiments, the effective amount is a therapeutically effective amount. In some embodiments, a therapeutically effective amount is an amount useful for the treatment and / or prevention of B cell neoplasms. In some embodiments, B-cell neoplasms are, but are not limited to, Hodgkin's lymphoma and many non-Hodgkin's lymphomas, such as diffuse large B-cell lymphoma, follicular lymphoma, mucosal-related lymphoid lymphoma (MALT), small lymphocytes. Sexual lymphoma (overlapping with chronic lymphocytic leukemia), mantle cell lymphoma (MCL), Berkitt lymphoma, medial large cell type B cell lymphoma, Waldenström macroglobulinemia, nodal marginal zone B cell lymphoma ( NMZL), splenic marginal zone lymphoma (SMZL), intravascular large B-cell lymphoma, primary exudative lymphoma and lymphoma-like granulomatosis. The effective amount of the compound can vary from about 0.001 mg / kg to about 1000 mg / kg in one or more doses over a day or days (depending on the mode of administration). In some embodiments, the effective amounts are from about 0.001 mg / kg to about 1000 mg / kg, from about 0.01 mg / kg to about 750 mg / kg, from about 0.1 mg / kg to about 500 mg / kg, about 1.0 mg / kg. It can vary from ~ about 250 mg / kg and from about 10.0 mg / kg to about 150 mg / kg.

The pharmaceutical compositions described herein can be prepared by any method known in the field of pharmacy. In general, such preparation methods associate the compounds of the invention (“active ingredients”) with carriers or excipients and / or one or more other auxiliary ingredients, and then the necessary and / or necessary. Alternatively, if desired, it comprises the steps of molding or packaging the product into the desired single or multiple dose units.

The pharmaceutical composition can be prepared, packaged and / or sold in bulk as a single unit dose and / or as multiple single unit doses. As used herein, a "unit dose" is a separate amount of a pharmaceutical composition that comprises a predetermined amount of active ingredient. The amount of active ingredient is generally equal to the dose of active ingredient that would be administered to the subject and / or a convenient fraction of such dose, eg, one-half or one-third of such dose. ..

The pharmaceutical compositions of the present invention may be included in or diluted in a pharmaceutically acceptable carrier. The term "pharmaceutically acceptable carrier" as used herein is one or more mixable fillers, diluents or other such substances, humans, or dogs, cats, and the like. Means suitable for administration to other mammals such as rats, mice or horses. The term "carrier" refers to a natural or synthetic organic or inorganic component that combines active ingredients for ease of application. Carriers can be mixed with and from the preparations of the invention in a manner such that there are no interactions that substantially impair the desired efficacy or stability. Suitable carriers for oral, subcutaneous, intravenous, intramuscular and other formulations can be found at Remington's Pharmaceutical Sciences (Mack Publishing Company, Easton, Pa).

The compounds and compositions provided herein are enteral (eg, oral), parenteral, intravenous, intramuscular, intraarterial, intramedullary, intrathecal, subcutaneous, intraventricular, transdermal, intradermal,. By any route, including rectal, intravaginal, intraperitoneal, topical (such as with powders, ointments, creams and / or drops), mucosa, nose, buccal, sublingual; intratracheal, bronchial and / or It can be administered by inhalation; and / or by oral spray, nasal spray and / or aerosol. Particularly conceived routes are oral administration, intravenous administration (eg, systemic intravenous administration), topical administration via blood and / or lymphatic supply, and / or direct administration to the affected area. In general, the most appropriate route of administration is the nature of the agent (eg, its stability in the gastrointestinal environment) and / or the condition of the subject (eg, whether the subject can tolerate oral administration). ) Will depend on a variety of factors.

The exact amount of compound required to achieve an effective amount can be determined on a subject-by-subject basis, eg, subject species, age and general condition, severity of side effects or disorders, identity of a particular compound, administration. It will be different depending on the style of. The desired dose is 3 times a day, 2 times a day, once a day, once every 2 days, once every 3 days, once a week, once every two weeks, once every three weeks, Alternatively, it can be delivered once every four weeks. In some embodiments, the desired dose is administered in multiple doses (eg, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or more). May be delivered using.

In some embodiments, the effective amount of compound for administration to 70 kg of adult humans once or more than once daily is from about 0.0001 mg to about 3000 mg, from about 0.0001 mg to about 2000 mg per unit dosage form. , About 0.0001 mg to about 1000 mg, about 0.001 mg to about 1000 mg, about 0.01 mg to about 1000 mg, about 0.1 mg to about 1000 mg, about 1 mg to about 1000 mg, about 1 mg to about 100 mg, about 10 mg to about 1000 mg Alternatively, it may contain from about 100 mg to about 1000 mg of the compound.

In some embodiments, the compounds of the invention are about 0.001 mg to about 100 mg, about 0.01 mg to about 50 mg, preferably about 0.1 mg per kg body weight of the subject per day in order to obtain the desired therapeutic effect. ~ About 40 mg, preferably about 0.5 mg to about 30 mg, about 0.01 mg to about 10 mg, about 0.1 mg to about 10 mg, and more preferably at dose levels sufficient to deliver about 1 mg to about 25 mg. It is administered once or more than once a day.

It will be appreciated that the dose ranges described herein provide guidance for adult administration of the provided pharmaceutical compositions. For example, the amount to be administered to a child or adolescent can be determined by a doctor or one of ordinary skill in the art and may be lower or the same as that administered to an adult.

The present invention will be further described with reference to the following examples. The example should never be interpreted as a further limitation. The entire contents of the prior art references cited throughout this application, including academic references, fermented patents, published patent applications, and concurrent patent applications, are incorporated herein by reference.

４−メチル−３−（（７−（（２−（トリメチルシリル）エトキシ）メチル）−７Ｈ−ピロロ［２，３−ｄ］ピリミジン−４‐イル）オキシ）安息香酸：ＤＭＳＯ（５ｍＬ）中に４−クロロ−７−（（２−（トリメチルシリル）エトキシ）メチル）−７Ｈ−ピロロ［２，３−ｄ］ピリミジン（２８４ｍｇ、１．０ｍｍｏｌ）、３−ヒドロキシ−４−メチル安息香酸（１５２ｍｇ、１．０ｍｍｏｌ）およびＫ_２ＣＯ_３（４１４ｍｇ、３．０ｍｍｏｌ）を混合し、１００℃で一晩攪拌した。次いで、反応混合物を室温まで冷却した。混合物を１ＮのＨＣｌ溶液で酸性化し、酢酸エチルで抽出した。有機相をブラインで洗浄し、Ｎａ_２ＳＯ_４で乾燥させ、濾過および濃縮した。粗生成物を、カラムクロマトグラフィーによって精製し、２９６ｍｇの生成物を無色の油状物質として得た。ＭＳ（ＥＳＩ）ｍ／ｚ４００（Ｍ＋Ｈ）^＋。

３−（（７Ｈ−ピロロ［２，３−ｄ］ピリミジン−４‐イル）オキシ）−Ｎ−（３−（２−シアノプロパン−２‐イル）フェニル）−４−メチルベンズアミド（Ｉ−１１）：ＣＨ_２Ｃｌ_２（３ｍＬ）中の４−メチル−３−（（７−（（２−（トリメチルシリル）エトキシ）メチル）−７Ｈ−ピロロ［２，３−ｄ］ピリミジン−４‐イル）オキシ）安息香酸（２００ｍｇ、０．５ｍｍｏｌ）、ＨＡＴＵ（２３０ｍｇ、０．６ｍｍｏｌ）、ＤＭＡＰ（７３ｍｇ、０．６ｍｍｏｌ）およびｉＰｒ_２ＮＥｔ（２２０ｕＬ、１．２５ｍｍｏｌ）の溶液へ２−（３−アミノフェニル）−２−メチルプロパニトリル（８０ｍｇ、０．５ｍｍｏｌ）を添加し、得られた混合物を室温で２４時間撹拌した。溶液をろ過して固体を除去し、カラムクロマトグラフィー（ジクロロメタン：メタノール＝１０：１）で濃縮および精製し、無色の油状物質として４５５ｍｇの生成物を産出した。ＣＨ_２Ｃｌ_２（５ｍＬ）中の得られた油状物質の溶液へＴＦＡを添加し、得られた混合物を室温で５時間撹拌した。溶液を真空で濃縮および乾燥させ、次いでＴＨＦ（４ｍＬ）および１ＮのＮａＯＨ溶液（４ｍＬ）に溶解した。反応混合物を２４時間攪拌し、酢酸エチルで抽出した。混合した有機相をブラインで洗浄し、Ｎａ_２ＳＯ_４で乾燥させ、次いで、ろ過および濃縮し、逆相ＨＰＬＣによって精製して１８５ｍｇ（９０％）の表題化合物を白色固体として得た。
Ａ−１７の精製

Examples The following examples are provided to allow a more complete understanding of the inventions described herein. The synthetic and biological examples described herein are provided to illustrate the compounds, pharmaceutical compositions and methods provided herein and are by no means construed as limiting their scope. Should not be.

Example 1. Preparation of compound Preparation of I-11

4-Methyl-3-((7-((2- (trimethylsilyl) ethoxy) methyl) -7H-pyrrolo [2,3-d] pyrimidin-4-yl) oxy) Benzoic acid : 4 in DMSO (5 mL) −Chloro-7-((2- (trimethylsilyl) ethoxy) methyl) -7H-pyrrolo [2,3-d] pyrimidine (284 mg, 1.0 mmol), 3-hydroxy-4-methylbenzoic acid (152 mg, 1. 0 mmol) and K ₂ CO ₃ (414 mg, 3.0 mmol) were mixed and stirred at 100 ° C. overnight. The reaction mixture was then cooled to room temperature. The mixture was acidified with 1N HCl solution and extracted with ethyl acetate. The organic phase was washed with brine, dried over Na ₂ SO ₄ , filtered and concentrated. The crude product was purified by column chromatography to give 296 mg of product as a colorless oil. MS (ESI) m / z400 (M + H) ⁺ .

3-((7H-pyrrolo [2,3-d] pyrimidin-4-yl) oxy) -N- (3- (2-cyanopropan-2-yl) phenyl) -4-methylbenzamide (I-11) : 4-Methyl-3-((7-((2- (trimethylsilyl) ethoxy) methyl) -7H-pyrrolo [2,3-d] pyrimidin-4-yl) oxy) in _{CH 2} Cl _{2 (3 mL)} 2- (3-Aminophenyl)-to a solution of benzoic acid (200 mg, 0.5 mmol), HATU (230 mg, 0.6 mmol), DMAP (73 mg, 0.6 mmol) and iPr _{2 NEt (220 uL, 1.25 mmol)} 2-Methylpropanitrile (80 mg, 0.5 mmol) was added and the resulting mixture was stirred at room temperature for 24 hours. The solution was filtered to remove the solid and concentrated and purified by column chromatography (dichloromethane: methanol = 10: 1) to yield 455 mg of product as a colorless oil. TFA was added to the solution of the obtained oily substance in CH ₂ Cl ₂ (5 mL) and the resulting mixture was stirred at room temperature for 5 hours. The solution was concentrated and dried in vacuo and then dissolved in THF (4 mL) and 1N NaOH solution (4 mL). The reaction mixture was stirred for 24 hours and extracted with ethyl acetate. The mixed organic phase was washed with brine, dried over Na ₂ SO ₄ , then filtered and concentrated and purified by reverse phase HPLC to give 185 mg (90%) of the title compound as a white solid.
Purification of A-17

3-((6-Chloropyrimidine-4-yl) oxy) -4-methylbenzoic acid : 4,6-dichloropyrimidine (150 mg, 1.0 mmol) and 3-hydroxy-4-methylbenzoic acid in acetone (2 mL) Sodium hydroxide was added to a solution of acid (152 mg, 1.0 mmol) and the reaction mixture was stirred at room temperature for 1 hour, which is the point where LC-MS analysis showed complete consumption of the starting material. The reaction mixture was extracted with ethyl acetate. The collected organic phase was washed with brine, dried over Na ₂ SO ₄ , then filtered and concentrated and purified by column chromatography to give 250 mg (90%) of the product as a white solid. MS (ESI) m / z 265 (M + H) ⁺ .

3-((6-chloropyrimidine-4-yl) oxy) -N- (4-((4-ethylpiperazin-1-yl) methyl) -3- (trifluoromethyl) phenyl) -4-methylbenzamide : 3-((6-chloropyrimidine-4-yl) oxy) -4-methylbenzoic acid (210 mg, 0.8 mmol), HATU (365 mg, 0.96 mmol), DMAP (117 mg) in CH ₂ Cl _{2 (4 mL)} , 0.96 mmol) and 4-((4-ethylpiperazin-1-yl) methyl) -3- (trifluoromethyl) aniline (230 mg, 0.8 mmol) in a solution of _{iPr 2 NEt (350 uL, 2.0 mmol).} Was added, and the resulting mixture was stirred for 24 hours at room temperature. The solution was filtered to remove the solid and concentrated and purified by column chromatography to give 360 mg (84%) of the product as a pale yellow oil. MS (ESI) m / z 534 (M + H) ⁺ .

3-((6-Aminopyrimidine-4-yl) oxy) -N- (4-((4-ethylpiperazin-1-yl) methyl) -3- (trifluoromethyl) phenyl) -4-methylbenzamide : _{A 2N solution of NH 3} in 10 ml of i-PrOH was added to 3-((6-chloropyrimidine-4-yl) oxy) -N- (4-((4-ethylpiperazin-1-yl) methyl) -3-3. It was added to (trifluoromethyl) phenyl) -4-methylbenzamide (270 mg, 0.5 mmol) and the reaction mixture was stirred at 75 ° C. for 48 hours, then cooled to room temperature and concentrated. The crude product was purified by column chromatography to give 120 mg of product as a colorless oil. MS (ESI) m / z 515 (M + H) ⁺ .

3-((6-acrylamide pyrimidine-4-yl) oxy) -N- (4-((4-ethylpiperazin-1-yl) methyl) -3- (trifluoromethyl) phenyl) -4-methylbenzamide ( A-17):
3-((6-Aminopyrimidine-4-yl) oxy) -N- (4-((4-ethylpiperazin-1-yl) methyl) -3-( Acryloyl chloride (8.9 uL, 0.11 mmol) was added to a solution of trifluoromethyl) phenyl) -4-methylbenzamide (51 mg, 0.1 mmol). The cooling bath was removed so that the mixture warmed to room temperature and stirring was continued for 30 minutes. The solution was then diluted in DMSO and purified by reverse phase HPLC to give 45 mg (80%) of A-17 as a white solid.

Compounds (A-1) to (A-16) and (A-18) were prepared in the same manner as A-17.

The characterization data for all final compounds are in the table below.

Example 2. Biological assay of compounds
In vitro Activity Assays The in vitro activity of the compounds described herein in inhibiting TAK1, HCK and other kinases was obtained using the Invitrogen Select Screening assay known in the art. Shows the IC ₅₀ values determined from this assay below.

Cell proliferation analysis
CellTiter-Glo® Luminescent Cell Survival Assay (Promega) was used to assess cell viability after treatment with the described compounds. Cells were seeded in 384-well plates using EL406 Combination Washer Dispenser (BioTek Instruments, Inc.) and the compounds were injected into cell culture medium using JANUS Automated Workstation (PerkinElmer Inc.). Cells were treated with a serially diluted inhibitor (20-0.04 μM) for 72 hours at 37 ° C. Luminescence was measured using a 2104 Envision® Multilabel Reader (PerkinElmer Inc.).

Apoptosis analysis of bone marrow neoplastic cells in primary patients
WM cells were treated with or without the compounds described herein. Cells were incubated at 37 ° C. at 0.01-4 uM with the compounds described herein. Apoptosis analysis was performed using annexin V / propidium iodide staining with Apoptosis Detection Kit I (BD Pharmingen). 1 × 10 ⁶ / well cells were treated with an inhibitor or corresponding control in a 24-well plate for approximately 24 hours. A minimum of 10,000 events were obtained using a BD ™ FACSCanto II flow cytometer and analyzed with BD FACS DIVA software.

Results Numerous compounds described herein exhibit inhibitory activity against TAK1, HCK, BTK and other kinases. It is shown in Tables 1 and 1a, an IC ₅₀ data of an exemplary in vitro of these compounds. Tables 2 and 2a show _{EC 50} values of the in vitro of these compounds.

Kinome Scan
Kinome Scan ™ (DiscoverRx) assay was performed on compounds (A-2) and (A-17) to determine inhibition of a broad panel of known kinases.

Results Table 3 shows KinomeScan (active site-specific competitive binding assay for measuring interactions between test compounds and individual kinases) data for each compound II-1 and I-13. Lower values indicate greater inhibition of a given kinase by the test compound. As shown, II-1 and I-13, along with the important targets HCK, include some including LOK, DDR1, JNK2, ZAK, IKK-alpha, BLK, p38-alpha, ABL1, LYN and STK36. Inhibited other kinases.

Kinative
Kinase selectivity of compounds (A-5) and (A-14) was evaluated using a chemical proteomic approach, named KiNativ, that detects 260 kinases in A375 cells (ActivX Biosciences). To search for intracellular targets of the compound, A375 cells are incubated with an inhibitor at a final concentration of 1 μM, followed by ATP that non-specifically labels conserved lysine on kinases and other nucleotide-dependent enzymes. -Looked for protection of the label with a biotin probe.

Results Table 4 shows that compound (A-5) contains a number of kinases, including Abl (> 90%), FYN (71.2%), LYN (87.8%), and ZAK (75.7%). It is shown to inhibit at 1 μM. Table 5 shows that compound (A-14) contains a large number of kinases at 1 μM, including Abl (> 90%), FYN (88.2%), LYN (85.7%) and ZAK (75.8%). Indicates to inhibit.

Example 3. p-BTK and p-Hck inhibition
Protocol for PhosFlow research
PhosFlow was performed to constitutively overexpress HCK in BCWM.1 cells for BTK-pY223 (BD Biosciences) and Hck-pY410 (Abcam). BCWM. 1 cell (BCWM.1_HCK-wt) and constitutively overexpressing the T338M mutant of HCK (BCWM.1_HCK-mu). The level of phosphorylation was detected in one cell. Cells were fixed in BD Phosflow Fix Buffer I (BD Biosciences) at 37 ° C. for 10 minutes and then washed twice with BD Phosflow Perm / Wash Buffer I (BD Biosciences). The cells were turbid in BD Phosflow Perm / Wash Buffer I at 10 million cells / ml and the antibody was aliquoted into a flow tube with 100 μl of cells. The cells were incubated at room temperature in the dark for 30 minutes. Cells were washed twice with BD Phosflow Perm / Wash Buffer I before performing flow analysis using a BD Phosflow BD ™ FACSCanto II flow cytometer.

Protocol for Apoptosis Analysis After treatment of bone marrow mononuclear cells A-5 and A-14 from 24-hour WM patients, apoptosis analysis of primary-lymphoplasmacytic cells (LPCs) of WM patients was performed. did. Apoptosis analysis was performed using Annexin V / propidium iodide staining and Apoptosis Detection Kit I (BD Pharmingen) in an LPC population gated with CD19-APC-cy7 antibody (BD Pharmingen).

result
In the PhosFlow study, both A-5 and A-14 were found in BCWM. BCWM. 1 cell and genetically engineered expression of Hck wild-type (-wt) and T338M gatekeeper mutations (-mu). It was shown to inhibit the phosphorylation of Hck and BTK in one cell at both 0.5 μM and 0.1 μM doses (shown in Tables 6 and 7, respectively). In addition, expression of Hck-wt or Hck-mu increases resistance to inhibition of both Hck and BTK phosphorylation by A-5 and A-14, and BCWM.1 cells expressing Hck-mu. Was presented with stronger resistance. As shown in Table 8, both A-5 and A-14 significantly induced apoptosis in primary LPC in WM patients compared to DMSO control.

Equalities and Claims In the claims, articles such as "a", "an" and "the" may be more than one or one unless indicated to be the opposite or otherwise apparent from the context. Can mean. Claims and descriptions that include an "or" between one or more members of a group are one of the members of the group unless indicated to the contrary or otherwise apparent from the context. If more than one, or all, is present in, used in, or otherwise associated with a given product or process, it is considered to be satisfied. The present invention includes aspects in which exactly one member of the group is present in a given product or process, is used in it, or is otherwise related thereto. The present invention includes aspects in which more than one member of the group is present in a given product or process, is used in it, or is otherwise associated therewith.

Moreover, the present invention is in all variations, combinations and combinations in which one or more limitations, elements, clauses, and descriptive terms from one or more of the listed claims are introduced into another claim. Includes permutations. For example, any claim that depends on another claim can be modified to include one or more limitations found in any other claim that depends on the same underlying claim. If the elements are presented as a list, for example in the Markush group formula, each subgroup of the elements is also disclosed and any element can be removed from the group. In general, when an invention, or aspect of an invention, is referred to as comprising a particular element and / or feature, then a particular aspect of the invention or aspect of the invention comprises or comprises such element and / or feature. It should be understood that it consists of the future. For the purposes of simplification, those aspects are not specifically described verbatim herein. It is also noted that the terms "comprising" and "containing" are intended to be open and allow the inclusion of additional elements or steps. If the range is indicated, the endpoint is included. Moreover, unless otherwise indicated or otherwise apparent from the context and understanding of one of ordinary skill in the art, a value represented as a range is any particular value or subrange within the range described in different aspects of the invention. Can be taken up to one tenth of the lower limit unit of the range, unless the context explicitly indicates otherwise.

The present application cites a variety of published patents, published patent applications, articles in academic literature and other publications, all of which are incorporated herein by reference. If there is a contradiction between any of the incorporated references and the present specification, the present specification governs. Further, any particular aspect of the invention that falls within the prior art is explicitly excluded from any one or more of the claims. Such embodiments are believed to be known to peers and may be excluded even if the exclusions are not explicitly stated herein. Any particular aspect of the invention can be excluded from any claim for any reason, whether or not it relates to the presence of prior art.

One of ordinary skill in the art will recognize many equivalents for the particular embodiments described herein, or will only be able to identify them using routine experimentation. The scope of aspects of the invention described herein is not intended to be limited to the above description, but rather is described in the appended claims. Those skilled in the art will appreciate that various modifications and modifications to this description may be made without departing from the spirit or scope of the invention as defined in the claims below.

Claims (24)

formula:

During the ceremony:
In ^{each case of RA} , independently, hydrogen, halogen, optionally substituted alkyl, optionally substituted carbocyclyl, -OR ^A1 , -N ( ^RA1 ) ₂ , -CN, -C (= O) ^RA1 , -C (= O) OR ^A1 , -C (= O) N ( ^RA1 ) ₂ , -NO ₂ , -NR ^A1 C (= O) ^RA1 , -NR ^A1 C (= O) OR ^A1 , -NR ^A1 S (= O) ₂ R ^A1 , -S (= O) ₂ R ^A1 or -S (= O) ₂ N ( ^RA1 ) ₂ ;
For each R ^B, is independently hydrogen, halogen, optionally substituted alkyl, the optionally substituted carbocyclyl, any substituted heterocyclyl, any substituted aryl, optionally substituted heteroaryl, -OR A1, ^{-N (R A1} ) ₂ , -CN, -C (= O) R ^A1 , -C (= O) OR ^A1 , -C (= O) N ( ^RA1 ) ₂ , -NO ₂ , -NR ^A1 C (= O) ^RA1 , -NR ^A1 C (= O) OR ^A1 , -NR ^A1 S (= O) ₂ ^RA1 , -S (= O) ₂ ^RA1 or -S (= O) ₂ N ( ^RA1 ) ₂ There, provided that at least one of ^{R B} is optionally substituted heterocyclyl, optionally substituted - _(CH 2) (heterocyclyl), optionally substituted - _{(CH 2)} 2 (heterocyclyl), or optionally substituted - _{(CH 2)} 3 ₍ Heterocyclyl);
For each R ^A1, independently, hydrogen, optional substituted acyl, the optionally substituted alkyl, the optionally substituted alkenyl, arbitrary substituted alkynyl, any substitution carbocyclyl, any substituted heterocyclyl, any substituted aryl, optionally Substituted heteroaryl, a nitrogen-protecting group if attached to a nitrogen atom, an oxygen-protecting group if attached to an oxygen atom, or a sulfur-protecting group if attached to a sulfur atom, or 2 The ^RA1 groups are linked to form an arbitrarily substituted heterocyclic ring;
Ring B is the formula:

Is;
^{Each case of RY} is independently a hydrogen, halogen or substituted or unsubstituted C _1-6 alkyl group;
For each of R ^X, independently, ^{R D,} optionally substituted carbocyclyl, optionally substituted heterocyclyl, are selected from the group consisting of optionally substituted heteroaryl, and ^{-N (R A1) (R Xa} ); however , at least one of ^{R _X,} -NH _2, -NH ^{(acyl), - N (R A1)} N (R A1) 2,

And
In ^{each case of RXa} , hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, -C (= O) ^RA1 , -C (= O) OR ^A1 , -C (= O) N ( ^RA1 ) ₂ , -S (= O) ^RA1 , -S (= O) N ( ^RA1 ) ₂ ,- S (= O) ₂ ^RA1 , -S (= O) ₂ OR ^A1 , -S (= O) ₂ N ( ^RA1 ) ₂ , -N ( ^RA1 ) ₂ or a nitrogen-protecting group ;
In ^{each case of RXc} , independently, hydrogen, halogen, optionally substituted alkyl, optionally substituted alkynyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted hetero _{^{aryl, -OR A1, -N (R A1}} ) 2, -SR A1, -CN, -C (= O) R A1, -C (= O) OR A1, -C (= O) N (R A1) ₂ , -NO ₂ , -N ₃ , -NR ^A1 C (= O) R ^A1 , -NR ^A1 C (= O) OR ^A1 , -NR ^A1 C (= O) N ( ^RA1 ) ₂ , -NR ^A1 S (= O) ₂ R ^A1 , -NR ^A1 S (= O) R ^A1 , -OC (= O) R ^A1 , -OC (= O) OR ^A1 , -OC (= O) N ( ^RA1 ) ₂ , -S (= O) R ^A1 , -S (= O) N ( ^RA1 ) ₂ , -S (= O) ₂ R ^A1 , and -S (= O) ₂ N ( ^RA1 ) _2. More selected;
k is 0, 1, 2, 3 or 4;
l is 1, 2, 3, 4 or 5;
-Q-U- is -NR ^A (C = O)-or-(C = O) NR ^A- ;
^RD is the equations (i-1) to (i-18):

Is the electrophile part of any one of
^RD1 is hydrogen, halogen, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbometricyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl,- CN, -NO ₂ , -OR ^D1a , -N ( ^RD1a ) ₂ , -SR ^D1a , -CH ₂ OR ^D1a , -CH ₂ N ( ^RD1a ) ₂ , -CH ₂ SR ^D1a , -C (= O) R ^D1a , -C (= O) OR ^D1a , -C (= O) SR ^D1a , -C (= O) N ( ^RD1a ) ₂ , -C (= S) R ^D1a , -C (= S) OR ^D1a , -C (= S) SR ^D1a , -C (= S) N ( ^RD1a ) ₂ , -C (= NR ^D1a ) R ^D1a , -C (= NR ^D1a ) OR ^D1a , -C (= NR ^D1a) ) SR ^D1a , and -C (= NR ^D1a ) N ( ^RD1a ) ₂ selected from the group, where ^{each appearance of R D1a} is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl. , Arbitrarily substituted alkynyl, arbitrarily substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or two R ^D1a groups are linked and optionally Form a heterocyclic ring substituted with;
^RD2 is hydrogen, halogen, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbometricyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl,- CN, -NO ₂ , -OR ^D2a , -N ( ^RD2a ) ₂ , -SR ^D2a , -CH ₂ OR ^D2a , -CH ₂ N ( ^RD2a ) ₂ , -CH ₂ SR ^D2a , -C (= O) R ^D2a , -C (= O) OR ^D2a , -C (= O) SR ^D2a , -C (= O) N ( ^RD2a ) ₂ , -C (= S) R ^D2a , -C (= S) OR ^D2a , -C (= S) SR ^D2a , -C (= S) N ( ^RD2a ) ₂ , -C (= NR ^D2a ) R ^D2a , -C (= NR ^D2a ) OR ^D2a , -C (= NR ^D2a) ) SR ^D2a , and -C (= NR ^D2a ) N ( ^RD2a ) ₂ selected from the group, where ^{each appearance of R D2a} is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl. , Arbitrarily substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or two R ^D2a groups are linked and optionally Form a heterocyclic ring substituted with;
R ^D3 is hydrogen, halogen, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbometricyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl,- CN, -NO ₂ , -OR ^D3a , -N ( ^RD3a ) ₂ , -SR ^D3a , -CH ₂ OR ^D3a , -CH ₂ N ( ^RD3a ) ₂ , -CH ₂ SR ^D3a , -C (= O) R ^D3a , -C (= O) OR ^D3a , -C (= O) SR ^D3a , -C (= O) N ( ^RD3a ) ₂ , -C (= S) R ^D3a , -C (= S) OR ^D3a , -C (= S) SR ^D3a , -C (= S) N ( ^RD3a ) ₂ , -C (= NR ^D3a ) R ^D3a , -C (= NR ^D3a ) OR ^D3a , -C (= NR ^D3a) ) SR ^D3a , and -C (= NR ^D3a ) N ( ^RD3a ) ₂ selected from the group, where ^{each appearance of R D3a} is independently hydrogen, optionally substituted alkyl, optionally substituted. Selected from the group consisting of alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or two R ^D3a groups are linked and Form an arbitrarily substituted heterocyclic ring;
Alternatively, ^RD1 and ^RD3 , or ^RD2 and ^RD3 , or ^RD1 and ^RD2 are linked to form an arbitrarily substituted carbocyclic ring or an arbitrarily substituted heterocyclic ring;
R ^D4 is a leaving group;
^RD5 is a hydrogen, substituted or unsubstituted C _1-6 alkyl, or nitrogen protecting group;
Y ^Z is -O-, -S-, or -NR ^D6- , where ^RD6 is a hydrogen, substituted or unsubstituted C _1-6 alkyl, or nitrogen protecting group;
a is 1 or 2; and z is 1, 2, 3, 4, 5 or 6;
Here, in the case of each of the nitrogen-protecting groups combined with the nitrogen atom to which the nitrogen-protecting group is bonded, formamide, acetamide, chloroacetamide, trichloroacetamide, trifluoroacetamide, and phenylaceta are independently used. Mido, 3-phenylpropaneamide, picolinamide, 3-pyridylcarboxamide, benzamide, p-phenylbenzamide, o-nitrophenylacetamide, o-nitrophenoxyacetamide, acetoacetamide, 3- (p-hydroxyphenyl) propane Amide, 3- (o-nitrophenyl) propaneamide, 2-methyl-2- (o-nitrophenoxy) propaneamide, 2-methyl-2- (o-phenylazophenoxy) propaneamide, 4-chlorobutaneamide, 3-Methyl-3-nitrobutaneamide, o-nitrocinnamide, o-nitrobenzamide, o- (benzoyloxymethyl) benzamide, methylcarbamate, ethylcarbamate, 9-fluorenylmethylcarbamate (Fmoc), 9- (2-) Sulfo) fluorenylmethylcarbamate, 9- (2,7-dibromo) fluorenylmethylcarbamate, 2,7-di-t-butyl- [9- (10,10-dioxo-10,10,10,10) -Tetrahydrothioxanthyl)] Methyl carbamate (DBD-Tmoc), 4-methoxyphenacil carbamate (Phenoc), 2,2,2-trichloroethyl carbamate (Troc), 2-trimethylsilylethyl carbamate (Teoc), 2-phenyl Ethyl carbamate (hZ), 1- (1-adamantyl) -1-methylethyl carbamate (Adpoc), 1,1-dimethyl-2-haloethyl carbamate, 1,1-dimethyl-2,2-dibromoethyl carbamate (DB) -T-BOC), 1,1-dimethyl-2,2,2-trichloroethyl carbamate (TCBOC), 1-methyl-1- (4-biphenylyl) ethyl carbamate (Bpoc), 1- (3,5-di) -T-Butylphenyl) -1-methylethylcarbamate (t-Bumeoc), 2- (2'-and 4'-pyridyl) ethylcarbamate (Pyoc), 2- (N, N-dicyclohexylcarboxamide) ethylcarbamate, t -Butyl carbamate (BOC), 1-adamantyl carbamate (Adoc), vinyl carbamate (Voc), allyl carbamate (Aloc), 1-isopropyla Lilcarbamate (Ipaoc), cinnamylcarbamate (Coc), 4-nitrocinnamylcarbamate (Noc), 8-quinolylcarbamate, N-hydroxypiperidinylcarbamate, alkyldithiocarbamate, benzylcarbamate (Cbz), p-methoxy Benzyl Carbamate (Moz), p-Nitrobenzyl Carbamate, p-Bromobenzyl Carbamate, p-Chlorobenzyl Carbamate, 2,4-Dichlorobenzyl Carbamate, 4-Methylsulfinyl benzyl Carbamate (Msz), 9-Anthylmethyl Carbamate, Diphenyl Methyl carbamate, 2-methylthioethyl carbamate, 2-methylsulfonyl ethyl carbamate, 2- (p-toluenesulfonyl) ethyl carbamate, [2- (1,3-dithianyl)] methyl carbamate (Dmoc), 4-methylthiophenyl carbamate ( Mtpc), 2,4-dimethylthiophenylcarbamate (Bmpc), 2-phosphonioethylcarbamate (Peoc), 2-triphenylphosphonioisopropylcarbamate (Ppoc), 1,1-dimethyl-2-cyanoethylcarbamate, p- (Dihydroxyboryl) benzyl carbamate, 5-benzoisoxazolyl methyl carbamate, 2- (trifluoromethyl) -6-chromonyl methyl carbamate (Tcroc), m-nitrophenyl carbamate, 3,5-dimethoxybenzyl carbamate, o -Nitrobenzyl carbamate, 3,4-dimethoxy-6-nitrobenzyl carbamate, phenyl (o-nitrophenyl) methyl carbamate, t-amyl carbamate, S-benzylthiocarbamate, p-cyanobenzyl carbamate, cyclobutyl carbamate, cyclohexyl carbamate , Cyclopentyl carbamate, cyclopropyl methyl carbamate, p-decyloxybenzyl carbamate, o- (N, N-dimethylcarboxamide) benzyl carbamate, 1,1-dimethyl-3- (N, N-dimethylcarboxamide) propyl carbamate, 1, 1-Dimethylpropynylcarbamate, di (2-pyridyl) methylcarbamate, 2-furanylmethylcarbamate, 2-iodoethylcarbamate, isobornylcarbamate, isobutylcarbamate, isonicotinylcarbamate, p- (p'-methoxyphenylazo) ) Benzyl carbame , 1-Methylcyclobutylcarbamate, 1-methylcyclohexylcarbamate, 1-methyl-1-cyclopropylmethylcarbamate, 1-methyl-1- (3,5-dimethoxyphenyl) ethylcarbamate, 1-methyl-1-( p-phenylazophenyl) ethyl carbamate, 1-methyl-1-phenylethyl carbamate, 1-methyl-1- (4-pyridyl) ethyl carbamate, phenyl carbamate, p- (phenylazo) benzyl carbamate, 2,4,6- Tri-t-butylphenylcarbamate, 4- (trimethylammonium) benzylcarbamate, 2,4,6-trimethylbenzylcarbamate, p-toluenesulfonamide (Ts), benzenesulfonamide, 2,3,6-trimethyl-4- Methoxybenzenesulfonamide (Mtr), 2,4,6-trimethoxybenzenesulfonamide (Mtb), 2,6-dimethyl-4-methoxybenzenesulfonamide (Pme), 2,3,5,6-tetramethyl- 4-methoxybenzenesulfonamide (Mte), 4-methoxybenzenesulfonamide (Mbs), 2,4,6-trimethylbenzenesulfonamide (Mts), 2,6-dimethoxy-4-methylbenzenesulfonamide (iMds), 2,2,5,7,8-Pentamethylchroman-6-sulfonamide (Pmc), methanesulfonamide (Ms), β-trimethylsilylethanesulfonamide (SES), 9-anthracenesulfonamide, 4- (4' , 8'-Dimethoxynaphthylmethyl) benzenesulfonamide (DNMBS), benzylsulfonamide, trifluoromethylsulfonamide, phenacylsulfonamide, 4,5-diphenyl-3-oxazoline-2-one, N-phthalimide, N- Dithiascusinimide (Dts), N-2,3-diphenylmaleimide, N-2,5-dimethylpyrrole, 5-substituted 1,3-dimethyl-1,3,5-triazacyclohexane-2-one, 5- Substitution 1,3-dibenzyl-1,3,5-triazacyclohexane-2-one, 1-substituted 3,5-dinitro-4-pyridone, N-methylamine, N-allylamine, N- [2- (trimethylsilyl) ) Ethoxy] Methylamine (SEM), N-3-acetoxypropylamine, N- (1-isopropyl-4-nitro-2-oxo-3-pyrrolin-3-yl) amine, N-benzylamine, N −Di (4-methoxyphenyl) methylamine, N-5-dibenzosverylamine, N-triphenylmethylamine (Tr), N-[(4-methoxyphenyl) diphenylmethyl] amine (MMTr), N-9- Phenylfluorenylamine (PhF), N-2,7-dichloro-9-fluorenylmethyleneamine, N-ferrocenylmethylamino (Fcm), N-2-picorylamino N'-oxide, N-1,1 -Dimethylthiomethyleneamine, N-benzylideneamine, N-p-methoxybenzideneamine, N-diphenylmethyleneamine, N-[(2-pyridyl) mesityl] methyleneamine, N- (N', N'-dimethylaminomethylene ) Amine, Np-nitrobenzylene amine, N-salicylideneamine, N-5-chlorosalicylideneamine, N- (5-chloro-2-hydroxyphenyl) phenylmethyleneamine, N-cyclohexylideneamine , N- (5,5-dimethyl-3-oxo-1-cyclohexenyl) amine, N-copper chelate, N-zinc chelate, N-nitroamine, N-nitrosoamine, amine N-oxide, diphenylphosphinamide (Dpp) , Dimethylthiophosphinamide (Mpt), diphenylthiophosphinamide (Ppt), dialkylphosphoramide, dibenzylphosphoramide, diphenylphosphoramide, benzenesulfenamide, o-nitrobenzenesulphenamide (Nps) , 2,4-Dinitrobenzene sulfenamide, pentachlorobenzene sulfenamide, 2-nitro-4-methoxybenzene sulfenamide, triphenylmethyl sulfenamide, and 3-nitropyridine sulfenamide (Npys). More selected; or two cases of a nitrogen-protecting group combined with a nitrogen atom to which the nitrogen-protecting group is attached are N, N'-isopropyridenediamines; or each case of a nitrogen-protecting group. Are independently -OH, -OR ^aa , -N (R ^cc ) ₂ , -C (= O) R ^aa , -C (= O) N (R ^cc ) ₂ , -CO ₂ R ^aa ,- SO ₂ R ^aa , -C (= NR ^cc ) R ^aa , -C (= NR ^cc ) OR ^aa , -C (= NR ^cc ) N (R ^cc ) ₂ , -SO ₂ N (R ^cc ) ₂ ,- SO ₂ R ^cc , -SO ₂ OR ^cc , -SOR ^aa , -C (= S) N (R ^cc ) ₂ , -C (= O) SR ^cc , -C (= S) SR ^cc , C _1-10 alkyl, C _2-10 alkenyl, C _2-10 alkynyl, From the _{group consisting of C 1-10} heteroalkyl, C _2-10 heteroalkenyl, C _2-10 heteroalkynyl, C _3-10 carbocyclyl, 3-14 member heterocyclyl, C _6-14 aryl, and 5-14 member heteroaryl. Selected, where each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl and heteroaryl are independently 0, 1, 2, 3, 4 or 5 Rs. Substituted with an ^{dd group;}
The oxygen protective groups are methyl, methoxylmethyl (MOM), methylthiomethyl (MTM), t-butylthiomethyl, (phenyldimethylsilyl) methoxymethyl (SMOM), benzyloxymethyl (BOM), p-methoxybenzyloxymethyl ( PMBM), (4-methoxyphenoxy) methyl (p-AOM), guaiacol methyl (GUM), t-butoxymethyl, 4-pentenyloxymethyl (POM), siloxymethyl, 2-methoxyethoxymethyl (MEM), 2, 2,2-Trichloroethoxymethyl, bis (2-chloroethoxy) methyl, 2- (trimethylsilyl) ethoxymethyl (SEMOR), tetrahydropyranyl (THP), 3-bromotetrahydropyranyl, tetrahydrothiopyranyl, 1-methoxy Cyclohexyl, 4-methoxytetrahydropyranyl (MTHP), 4-methoxytetrahydrothiopyranyl, 4-methoxytetrahydrothiopyranyl S, S-dioxide, 1-[(2-chloro-4-methyl) phenyl] -4- Methoxypiperidine-4-yl (CTMP), 1,4-dioxan-2-yl, tetrahydrofuranyl, tetrahydrothiofuranyl, 2,3,3a,4,5,6,7,7a-octahydro-7,8, 8-trimethyl-4,7-methanobenzofuran-2-yl, 1-ethoxyethyl, 1- (2-chloroethoxy) ethyl, 1-methyl-1-methoxyethyl, 1-methyl-1-benzyloxyethyl, 1 -Methyl-1-benzyloxy-2-fluoroethyl, 2,2,2-trichloroethyl, 2-trimethylsilylethyl, 2- (phenylselenyl) ethyl, t-butyl, allyl, p-chlorophenyl, p-methoxyphenyl , 2,4-Dinitrophenyl, benzyl (Bn), p-methoxybenzyl, 3,4-dimethoxybenzyl, o-nitrobenzyl, p-nitrobenzyl, p-halobenzyl, 2,6-dichlorobenzyl, p-cyanobenzyl , P-phenylbenzyl, 2-picoryl, 4-picoryl, 3-methyl-2-picoryl N-oxide, diphenylmethyl, p, p'-dinitrobenzhydryl, 5-dibenzosveryl, triphenylmethyl, α- Naftyldiphenylmethyl, p-methoxyphenyldiphenylmethyl, di (p-methoxyphenyl) phenylmethyl, tri (p-methoxyphenyl) methyl, 4- (4'-bromophenacyloxyphenyl) diphenylmethi Le, 4,4', 4''-tris (4,5-dichlorophthalimidephenyl) methyl, 4,4', 4''-tris (levlinoyloxyphenyl) methyl, 4,4', 4'' -Tris (benzoyloxyphenyl) methyl, 1,1-bis (4-methoxyphenyl) -1'-pyrenylmethyl, 9-anthril, 9- (9-phenyl) xanthenyl, 9- (9-phenyl-10-oxo) Anthryl, 1,3-benzodithiolan-2-yl, benzoisothiazolyl S, S-dioxide, trimethylsilyl (TMS), triethylsilyl (TES), triisopropylsilyl (TIPS), dimethylisopropylsilyl (IPDMS), diethylisopropyl Cyril (DEIPS), dimethylhexylsilyl, t-butyldimethylsilyl (TBDMS), t-butyldiphenylsilyl (TBDPS), tribenzylsilyl, tri-p-xysilylsilyl, triphenylsilyl, diphenylmethylsilyl (DPMS), t- Butylmethoxyphenylsilyl (TBMPS), -R ^aa , -N (R ^bb ) ₂ , -C (= O) SR ^aa , -C (= O) R ^aa , -CO ₂ R ^aa , -C (= O) N (R ^bb ) ₂ , -C (= NR ^bb ) R ^aa , -C (= NR ^bb ) OR ^aa , -C (= NR ^bb ) N (R ^bb ) ₂ , -S (= O) R ^aa , -SO ₂ R ^aa , -Si (R ^aa ) ₃ , -P (R ^cc ) ₂ , -P (= O) (R ^aa ) ₂ , -P (= O) (OR ^cc ) ₂ , and -P ( = O) (NR ^bb ) _{Selected from the group consisting of 2} ; or in the case of each of the oxygen protecting groups combined with the oxygen atom to which the oxygen protecting group is attached, independently, formate, benzoylformate. , Acetate, chloroacetate, dichloroacetate, trichloroacetate, trifluoroacetate, methoxyacetate, triphenylmethoxyacetate, phenoxyacetate, p-chlorophenoxyacetate, 3-phenylpropionate, 4-oxopentanoate (levulinate), 4 , 4- (ethylenedithio) pentanoate (levrinoyldithioacetal), pivaloate, adamantoate, crotonate, 4-methoxycrotonate, benzoate, p-phenylbenzoate, 2,4,6-trimethylbenzoate (mesitoate) Tylcarbonate, 9-fluorenylmethylcarbonate (Fmoc), ethylcarbonate, 2,2,2-trichloroethylcarbonate (Troc), 2- (trimethylsilyl) ethylcarbonate (TMSEC), 2- (phenyl) Sulfonyl) ethylcarbonate (Psec), 2- (triphenylphosphonio) ethylcarbonate (Peoc), isobutylcarbonate, vinylcarbonate, allylcarbonate, t-butylcarbonate (BOC), p-nitrophenylcarbone Nate, benzylcarbonate, p-methoxybenzylcarbonate, 3,4-dimethoxybenzylcarbonate, o-nitrobenzylcarbonate, p-nitrobenzylcarbonate, S-benzylthiocarbonate, 4-ethoxy-1-naphthyl Carbonate, Methyldithiocarbonate, 2-iodobenzoate, 4-azidobutyrate, 4-nitro-4-methylpentanoate, o- (dibromomethyl) benzoate, 2-formylbenzenesulfonate, 2- (methylthiomethoxy) Ethylcarbonate, 4- (methylthiomethoxy) butylate, 2- (methylthiomethoxymethyl) benzoate, 2,6-dichloro-4-methylphenoxyacetate, 2,6-dichloro-4- (1,1,3,3-) Tetramethylbutyl) phenoxyacetate, 2,4-bis (1,1-dimethylpropyl) phenoxyacetate, chlorodiphenylacetate, isobutyrate, monosuccinoate, (E) -2-methyl-2-butenoate, α-naphthoate, Niterate , N , N, N', N'-tetramethylphosphologiamidate , N -phenylcarbamate, borate, dimethylphosphinochi oil , 2,4-dinitrophenylsulfenate, sulfate, methanesulfonate (mesylate) , Benzylsulfonate, and tosilate (Ts);
Sulfur protecting groups are -R ^aa , -N (R ^bb ) ₂ , -C (= O) SR ^aa , -C (= O) R ^aa , -CO ₂ R ^aa , -C (= O) N (R). ^bb ) ₂ , -C (= NR ^bb ) R ^aa , -C (= NR ^bb ) OR ^aa , -C (= NR ^bb ) N (R ^bb ) ₂ , -S (= O) R ^aa , -SO ₂ R ^aa , -Si (R ^aa ) ₃ , -P (R ^cc ) ₂ , -P (= O) (R ^aa ) ₂ , -P (= O) (OR ^cc ) ₂ , and -P (= O) (NR ^bb ) Selected from the group consisting of _2;
In ^{each case of Raa} , independently, C _1-10 alkyl, C _1-10 perhaloalkyl, C _2-10 alkenyl, C _2-10 alkynyl, hetero C _1-10 alkyl, hetero C _2-10 alkenyl. , hetero _{C 2-10 alkynyl, C 3-10} carbocyclyl, 3-14 membered _{heterocyclyl,} or is selected from the group consisting of _{C 6-14} aryl, and 5-14 membered heteroaryl, or two ^{R aa} groups , Linked to form a 3- to 14-membered heterocyclyl or 5- to 14-membered heteroaryl ring, where the respective alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl and heteroaryl Independently substituted with 0, 1, 2, 3, 4 or 5 ^{Rdd groups;}
In ^{each case of R bb} , independently, hydrogen, -OH, -OR ^aa , -N (R ^cc ) ₂ , -CN, -C (= O) R ^aa , -C (= O) N (R). ^cc ) ₂ , -CO ₂ R ^aa , -SO ₂ R ^aa , -C (= NR ^cc ) OR ^aa , -C (= NR ^cc ) N (R ^cc ) ₂ , -SO ₂ N (R ^cc ) ₂ , -SO ₂ R ^cc , -SO ₂ OR ^cc , -SOR ^aa , -C (= S) N (R ^cc ) ₂ , -C (= O) SR ^cc , -C (= S) SR ^cc , -P ( = O) ( ^Raa ) ₂ , -P (= O) (NR ^cc ) ₂ , C _1-10 alkyl, C _1-10 perhaloalkyl, C _2-10 alkenyl, C _2-10 alkynyl, hetero C _1- Is it selected from the group consisting of ₁₀ alkyl, hetero C _2-10 alkenyl, hetero C _2-10 alkynyl, C _3-10 carbocyclyl, 3-14 member heterocyclyl, C _{6-14 aryl, and 5-14 member heteroaryl?} , Or two R ^bb groups are linked to form a 3- to 14-membered heterocyclyl or 5- to 14-membered heteroaryl ring, where the respective alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl. , Heterocyclyls, aryls and heteroaryls are independently substituted with 0, 1, 2, 3, 4 or 5 R ^{dd groups;}
In ^{each case of R cc} , independently, hydrogen, C _1-10 alkyl, C _1-10 perhaloalkyl, C _2-10 alkenyl, C _2-10 alkynyl, hetero C _1-10 alkyl, hetero C _{2- Selected from the group consisting of 10} alkenyl, hetero C _2-10 alkynyl, C _3-10 carbocyclyl, 3-14 member heterocyclyl, C _6-14 aryl, and 5-14 member heteroaryl, or 2 R ^ccs. The groups are linked to form a 3- to 14-membered heterocyclyl or 5- to 14-membered heteroaryl ring, where the respective alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl and heteroaryl Is independently substituted with 0, 1, 2, 3, 4 or 5 ^{Rdd groups;}
In ^{each case of R dd} , independently, halogen, -CN, -NO ₂ , -N ₃ , -SO ₂ H, -SO ₃ H, -OH, -OR ^ee , -ON (R ^ff ) ₂ , _{^{-N (R ff) 2, -N}} (R ff) 3 + X -, -N (OR ee) R ff, -SH, -SR ee, -SSR ee, -C (= O) R ee, -CO ₂ H, -CO ₂ R ^ee , -OC (= O) R ^ee , -OCO ₂ R ^ee , -C (= O) N (R ^ff ) ₂ , -OC (= O) N (R ^ff ) ₂ , -NR ^ff C (= O) R ^ee , -NR ^ff CO ₂ R ^ee , -NR ^ff C (= O) N (R ^ff ) ₂ , -C (= NR ^ff ) OR ^ee , -OC (= NR ^ff) ) R ^ee , -OC (= NR ^ff ) OR ^ee , -C (= NR ^ff ) N (R ^ff ) ₂ , -OC (= NR ^ff ) N (R ^ff ) ₂ , -NR ^ff C (= NR ^ff) ) N (R ^ff ) ₂ , -NR ^ff SO ₂ R ^ee , -SO ₂ N (R ^ff ) ₂ , -SO ₂ R ^ee , -SO ₂ OR ^ee , -OSO ₂ R ^ee , -S (= O) R ^ee , -Si (R ^ee ) ₃ , -OSi (R ^ee ) ₃ , -C (= S) N (R ^ff ) ₂ , -C (= O) SR ^ee , -C (= S) SR ^ee , -SC (= S) SR ^ee , -P (= O) ( ^Ree ) ₂ , -OP (= O) ( ^Ree ) ₂ , -OP (= O) (OR ^ee ) ₂ , C _1-6 alkyl , C _1-6 perhaloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, hetero C _1-6 alkyl, hetero C _2-6 alkenyl, hetero C _2-6 alkynyl, C _3-10 carbocyclyl, 3-10 Selected from the group consisting of member heterocyclyls, C _6-10 aryls, 5-10 membered heteroaryls, where the respective alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl and heteroaryl are , Independently substituted with 0, 1, 2, 3, 4 or 5 R ^gg groups, or the two Geminal R ^dd substituents are linked to form = O or = S. May;
In ^{each case of Ree} , independently, C _1-6 alkyl, C _1-6 perhaloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, hetero C _1-6 alkyl, hetero C _2-6 alkenyl. , Hetero C _2-6 alkynyl, C _3-10 carbocyclyl, C _6-10 aryl, 3-10 member heterocyclyl, and 3-10 member heteroaryl, where the respective alkyl, alkenyl, alkynyl, Heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl and heteroaryl are independently substituted with ^{0, 1, 2, 3, 4 or 5 Rgg groups;}
In ^{each case of R ff} , hydrogen, C _1-6 alkyl, C _1-6 perhaloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, hetero C _1-6 alkyl, hetero C _{2- Selected from the group consisting of 6} alkenyl, hetero C _2-6 alkynyl, C _3-10 carbocyclyl, 3-10 member heterocyclyl, C _6-10 aryl, and 5-10 member heteroaryl, or 2 R ^ff. The groups are linked to form a 3- to 10-membered heterocyclyl or 5- to 10-membered heteroaryl ring, where the respective alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl and heteroaryl Is independently substituted with 0, 1, 2, 3, 4 or 5 ^{Rgg groups;}
In ^{each case of R gg} , independently, halogen, -CN, -NO ₂ , -N ₃ , -SO ₂ H, -SO ₃ H, -OH, -OC _1-6 alkyl, -ON (C _{1). -6 alkyl)} 2, -N _{(C 1-6 alkyl)} 2, -N _{(C 1-6 ^{alkyl) 3 + X -, -NH (}} C 1-6 _{^{alkyl) 2 + X -, -NH 2}} (C _{^{6alkyl) + X -, -NH 3 +}} X -, -N (OC 1-6 _{alkyl) (C 1-6 alkyl), - N (OH) (} C 1-6 alkyl), - NH (OH _), - SH, _{-SC 1-6} alkyl, -SS _{(C 1-6 alkyl), - C (= O)} (C 1-6 _{alkyl), - CO 2 H, -CO} 2 (C 1-6 alkyl ), -OC (= O) (C _1-6 alkyl), -OCO ₂ (C _1-6 alkyl), -C (= O) NH ₂ , -C (= O) N (C _1-6 alkyl) ₂ , -OC (= O) NH (C _1-6 alkyl), -NHC (= O) (C _1-6 alkyl), -N (C _1-6 alkyl) C (= O) (C _1-6) Alkyl), -NHCO ₂ (C _1-6 alkyl), -NHC (= O) N (C _1-6 alkyl) ₂ , -NHC (= O) NH (C _1-6 alkyl), -NHC (= O) ) NH ₂ , -C (= NH) O (C _1-6 alkyl), -OC (= NH) (C _1-6 alkyl), -OC (= NH) OC _1-6 alkyl, -C (= NH) ) N (C _1-6 alkyl) ₂ , -C (= NH) NH (C _1-6 alkyl), -C (= NH) NH ₂ , -OC (= NH) N (C _1-6 alkyl) ₂ , -OC (NH) NH (C _1-6 alkyl), -OC (NH) NH ₂ , -NHC (NH) N (C _1-6 alkyl) ₂ , -NHC (= NH) NH ₂ , -NHSO _{2 (C 1-6 alkyl), - SO 2 N (C} 1-6 _{alkyl) 2, -SO 2 NH (C} 1-6 _{alkyl), - SO 2 NH 2,} -SO 2 C 1-6 alkyl, -SO ₂ OC _1-6 alkyl, -OSO ₂ C _1-6 alkyl, _{-SOC 1-6} alkyl, -Si _{(C 1-6 alkyl)} 3, -OSi _{(C 1-6 alkyl)} 3, -C (= S ) N (C _1-6 alkyl) ₂ , C (= S) NH (C _1-6 alkyl), C (= S) NH ₂ , -C (= O) S (C _1-6 alkyl),- C (= S) SC _1-6 alkyl, -SC (= S) SC _1-6 alkyl, -P (= O) (C _1-6 alkyl) ₂ , -OP (= O) (C _1-6 alkyl ) ₂ , -OP (= O) (OC _1-6 alkyl) ₂ , C _1-6 alkyl, C _1-6 perhaloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, hetero C _1-6 alkyl, Hetero C _2-6 alkenyl, Hetero C _2-6 alkynyl, C _3-10 Carbocyclyl, C _6-10 aryl, 3 to 10 member heterocyclyl, 5 to 10 member heteroaryl; or 2 Geminal R ^gg Substituents may be linked to form = O or = S;
X ^- each case is an counterion; and the leaving group, halogen, alkoxycarbonyloxy, aryloxycarbonyloxy, alkanesulfonyloxy, arene sulfonyloxy, alkyl - alkylcarbonyloxy, arylcarbonyloxy, aryloxy, methoxy , N, O-dimethylhydroxylamino, pixyl, -NO ₂ , trialkylammonium, aryliodonium salts, p-bromobenzenesulfonyl, 2-nitrobenzenesulfonyl, epoxides, and -OSO ₂ R ^LG1 selected from the group. R ^LG1 is selected from the group consisting of optionally substituted alkyl, optionally substituted alkenyl, optionally substituted heteroalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl, and optionally substituted heteroarylalkyl. Be done,
Compound, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer or isotope-labeled derivative thereof. -Q-U-

The compound according to claim 1, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer or isotope-labeled derivative thereof. .. Equation (A1):

The compound according to claim 1, which is a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer or isotope-labeled derivative thereof. Equation (A1-a):

Or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer or isotope-labeled derivative thereof,
The compound according to claim 3. Equation (A1-b):

Or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer or isotope-labeled derivative thereof.
During the ceremony:
R ^Xa1 is hydrogen, optionally substituted alkyl, optionally substituted alkyne, optionally substituted alkynyl, optionally substituted carbometricyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, -C (= O) ^RA1. , -C (= O) OR ^A1 , -C (= O) N ( ^RA1 ) ₂ , -S (= O) ^RA1 , -S (= O) N ( ^RA1 ) ₂ , -S (= O) ) ₂ ^RA1 , -S (= O) ₂ OR ^A1 , -S (= O) ₂ N ( ^RA1 ) ₂ , -N ( ^RA1 ) ₂ or a nitrogen-protecting group,
The compound according to claim 3. Equation (A1-c):

Or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer or isotope-labeled derivative thereof.
During the ceremony:
R ^Xa1 is hydrogen, optionally substituted alkyl, optionally substituted alkyne, optionally substituted alkynyl, optionally substituted carbometricyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, -C (= O) ^RA1. , -C (= O) OR ^A1 , -C (= O) N ( ^RA1 ) ₂ , -S (= O) ^RA1 , -S (= O) N ( ^RA1 ) ₂ , -S (= O) ) ₂ ^RA1 , -S (= O) ₂ OR ^A1 , -S (= O) ₂ N ( ^RA1 ) ₂ , -N ( ^RA1 ) ₂ or a nitrogen-protecting group,
The compound according to claim 3. Equation (A1-d):

Or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer or isotope-labeled derivative thereof,
The compound according to claim 3. Equation (A2):

The compound according to claim 1, which is a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer or isotope-labeled derivative thereof. Equation (A2-a):

Or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer or isotope-labeled derivative thereof,
The compound according to claim 8. Equation (A2-b):

Or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer or isotope-labeled derivative thereof.
During the ceremony:
R ^Xa1 is hydrogen, optionally substituted alkyl, optionally substituted alkyne, optionally substituted alkynyl, optionally substituted carbometricyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, -C (= O) ^RA1. , -C (= O) OR ^A1 , -C (= O) N ( ^RA1 ) ₂ , -S (= O) ^RA1 , -S (= O) N ( ^RA1 ) ₂ , -S (= O) ) ₂ ^RA1 , -S (= O) ₂ OR ^A1 , -S (= O) ₂ N ( ^RA1 ) ₂ , -N ( ^RA1 ) ₂ or a nitrogen-protecting group,
The compound according to claim 8. Equation (A2-c):

Or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer or isotope-labeled derivative thereof.
During the ceremony:
R ^Xa1 is hydrogen, optionally substituted alkyl, optionally substituted alkyne, optionally substituted alkynyl, optionally substituted carbometricyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, -C (= O) ^RA1. , -C (= O) OR ^A1 , -C (= O) N ( ^RA1 ) ₂ , -S (= O) ^RA1 , -S (= O) N ( ^RA1 ) ₂ , -S (= O) ) ₂ ^RA1 , -S (= O) ₂ OR ^A1 , -S (= O) ₂ N ( ^RA1 ) ₂ , -N ( ^RA1 ) ₂ or a nitrogen-protecting group,
The compound according to claim 8. Equation (A2-d):

Or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer or isotope-labeled derivative thereof,
The compound according to claim 8. ^RD is

Selected from the group consisting of
The compound according to claim 1 or 2, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer or isotope-labeled derivative thereof. The compound according to any one of claims 1 to 13, wherein at least one ^RA is a substituted or unsubstituted C _{1-6 alkyl, or a pharmaceutically acceptable salt, solvate, water thereof.} Japanese, polymorphic, co-crystal, tautomer, steric isomer or isotope-labeled derivative. At least one of R ^B group, a substituted or unsubstituted C _1-6 alkyl, A compound according to any one of claims 1 to 14 or a pharmaceutically acceptable salt, Hydrate, polymorph, co-crystal, tautomer, stereoisomer or isotope-labeled derivative. One R ^B group, a substituted or unsubstituted -CH 2 - _{(piperazinyl),} substituted or unsubstituted imidazolyl, substituted or unsubstituted piperazinyl or substituted or unsubstituted morpholine, or any of claims 1 to 15 one The compound according to the section, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, steric isomer or isotope-labeled derivative thereof. formula:

Or

Compound, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer or isotope-labeled derivative thereof. The compound according to any one of claims 1 to 17, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer or isotope label thereof. A pharmaceutical composition comprising the resulting derivative and a pharmaceutically acceptable excipient. The pharmaceutical composition according to claim 18, for use in the treatment of B cell neoplasms in a subject. The pharmaceutical composition according to claim 19, wherein the B cell neoplasm is Hodgkin lymphoma. The pharmaceutical composition according to claim 19, wherein the B cell neoplasm is a non-Hodgkin's lymphoma. B-cell neoplasms are diffuse large B-cell lymphoma, follicular lymphoma, mucosal-related lymphoid lymphoma (MALT), small lymphocytic lymphoma, mantle cell lymphoma (MCL), barkit lymphoma, mediastinal large cell type B-cell lymphoma, nodular marginal zone B-cell lymphoma (NMZL), splenic marginal zone lymphoma (SMZL), intravascular large B-cell lymphoma, primary exudative lymphoma, or lymphoma-like granulomatosis, claim 19. The pharmaceutical composition according to 19. The pharmaceutical composition according to claim 19, wherein the B cell neoplasm is Waldenstrem macrogamma globulinemia. Container, compound according to any one of claims 1 to 17, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer or isotope thereof. A kit comprising a body-labeled derivative or the pharmaceutical composition according to any one of claims 18-23, and a description for use in the subject.

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